bluuebunny/crossref_metadata_2025 huggingface dataset:
‘COLUMBANUS WORE A SINGLE COWL, NOT A DOUBLE ONE’: THE VITA DEICOLI AND THE LEGACY OF COLUMBANIAN MONASTICISM AT THE TURN OF THE FIRST MILLENNIUM
Authors: VANDERPUTTEN STEVEN
Published: November 2021

This article analyses the Life of St. Deicolus of Lure, a monastery in the Alsace region of east France, written by the cleric Theodoric in the 970s or 980s. It argues that the text contains a notable amount of information on the existence, methodology, and limitations of an ill-understood aspect of monastic integration around the year 1000. Relying on an analysis of the narrative's second prologue as well as scattered comments elsewhere in the text, it reconstructs three phenomena. The first is attempts to (re-)establish a Luxeuil-centered imagined community of institutions with a shared Columbanian legacy through the creation and circulation of hagiographic narratives. A second is the co-creation across institutional boundaries of texts and manuscripts that were designed to facilitate these integration attempts. And the third phenomenon is the limits of this integration effort, which did not tempt those involved to propose the establishment of a distinct ‘neo-Columbanian’ observance. As such, the Life represents an attempt to reconcile the legacy of Columbanus and his real or alleged followers as celebrated at late tenth-century Luxeuil and Lure with a contemporary understanding of reformed Benedictine identity.
EL TRATADO SERPENS ILLE VETERNOSVS (CPL 1263) ATRIBUIDO A JULIÁN DE TOLEDO: ESTUDIO, EDICIÓN Y TRADUCCIÓN
Authors: MARTÍN-IGLESIAS JOSÉ CARLOS , IRANZO-ABELLÁN SALVADOR
Published: November 2021

El códice Roma, Biblioteca Casanatense, 641, conserva, en su Sector II (del s. x y procedente de la catedral de Benevento) un tratado sin título sobre el destino del alma humana después de la muerte del cuerpo, conocido tradicionalmente como Vtrum animae de humanis corporibus exeuntes mox deducantur ad gloriam uel ad poenam an exspectent diem iudicii sine gloria et poena (CPL 1263), aunque en este artículo es denominado Serpens ille ueternosus. Esta obra sólo ha conocido una edición completa, publicada por Angelo Mai en 1833, quien, sin embargo, no consultó el manuscrito de la Casanatense, sino que trabajó sobre los materiales inéditos de Lorenzo Alessandro Zaccagni († 1712), prefecto de la Biblioteca Apostolica Vaticana. Una parte de la crítica ha querido identificar esta obra con el perdido Libellus de remediis blasphemiae del obispo Julián de Toledo (680–690). El estudio interno del texto lleva a pensar, no obstante, tal y como sugirió José Madoz, que se trata de un escrito redactado en el noroeste de la Península Ibérica hacia el último tercio del s. viii. El presente artículo revisa los distintos argumentos sobre la autoría y la datación del tratado Serpens ille ueternosus, estudia sus fuentes y el testimonio de Alcuino sobre una hejería similar a la criticada en el citado tratado, y ofrece la primera edición crítica del texto junto con su traducción.
Support for a “Jelly Sandwich” Model of the Tibetan Plateau
Authors: Rehnberg Morgan
Published: November 2021

Computer modeling constrained by positional data collected in the aftermath of the 2008 Wenchuan earthquake indicates the lower crust is less viscous than the upper mantle below it.
Space Weather Observations With InSight
Authors: Mittelholz A. , Johnson C. L. , Fillingim M. , Joy S. P. , Espley J. , Halekas J. , Smrekar S. , Banerdt W. B.
Published: November 2021

Solar activity, in the form of coronal mass ejections and corotating interaction regions, results in changes in the solar wind that propagate out through the solar system and interact with the magnetic field environments of planets. Such phenomena have been observed to affect the magnetic field and plasma around Mars as seen from orbit. However, no surface observations have previously been possible because of the absence of ground‐based instrumentation. Here, for the first time, we observe the effects of increased solar activity with the magnetometer on the InSight mission in December 2020. We find several days of increased activity including magnetic field fluctuations at periods of minutes to hours. Although only the flanks of this relatively weak coronal mass ejection hit Mars, the observed effects provide insight into how solar activity alters magnetic fields at the surface.
Seismic Structure of the St. Paul Fracture Zone and Late Cretaceous to Mid Eocene Oceanic Crust in the Equatorial Atlantic Ocean Near 18°W
Authors: Growe Kevin , Grevemeyer Ingo , Singh Satish C. , Marjanović Milena , Gregory Emma P. M. , Papenberg Cord , Vaddineni Venkata , Gómez de la Peña Laura , Wang Zhikai
Published: November 2021

Plate tectonics characterize transform faults as conservative plate boundaries where the lithosphere is neither created nor destroyed. In the Atlantic, both transform faults and their inactive traces, fracture zones, are interpreted to be structurally heterogeneous, representing thin, intensely fractured, and hydrothermally altered basaltic crust overlying serpentinized mantle. This view, however, has recently been challenged. Instead, transform zone crust might be magmatically augmented at ridge‐transform intersections before becoming a fracture zone. Here, we present constraints on the structure of oceanic crust from seismic refraction and wide‐angle data obtained along and across the St. Paul fracture zone near 18°W in the equatorial Atlantic Ocean. Most notably, both crust along the fracture zone and away from it shows an almost uniform thickness of 5–6 km, closely resembling normal oceanic crust. Further, a well‐defined upper mantle refraction branch supports a normal mantle velocity of 8 km/s along the fracture zone valley. Therefore, the St. Paul fracture zone reflects magmatically accreted crust instead of the anomalous hydrated lithosphere. Little variation in crustal thickness and velocity structure along a 200 km long section across the fracture zone suggests that distance to a transform fault had negligible impact on crustal accretion. Alternatively, it could also indicate that a second phase of magmatic accretion at the proximal ridge‐transform intersection overprinted features of starved magma supply occurring along the St. Paul transform fault.
The Economic and Environmental Benefits of Partial Leasing of Agricultural Water Rights
Authors: Khanal Rajendra , Brady Michael P. , Stöckle Claudio O. , Rajagopalan Kirti , Yoder Jonathan , Barber Michael E.
Published: November 2021

Balancing out‐of‐stream water demands and ecological instream flows is a difficult challenge in watershed‐scale management. Many watersheds already experience acute and chronic water shortages during average runoff years and may face more frequent and severe droughts in some locations due to climate and demographic change. Water markets may mitigate the economic consequences of shortages, but their potential is limited by the prevalence of all‐or‐nothing irrigate‐or‐fallow crop water use strategies. Irrigation water generally provides diminishing returns for crop productivity, so it may be possible to reduce water application at the margin with only a small loss in crop production, creating water savings that could be leased for other uses. We explore this scenario by combining a crop growth and hydrology (CropSyst) model with an economic model of farm profits and water trading, and apply it to the Walla Walla Basin in Washington State. Our results suggest that partial leasing of water rights through a deficit‐irrigation strategy could economically benefit annual crop growers while meaningfully increasing water availability for stream flow augmentation.
Long‐Term Mississippi River Trends Expose Shifts in the River Load Response to Watershed Nutrient Balances Between 1975 and 2017
Authors: Stackpoole Sarah , Sabo Robert , Falcone James , Sprague Lori
Published: November 2021

Excess nutrients transported by the Mississippi River (MR) contribute to hypoxia in the Gulf of Mexico. Nutrient balances are key drivers to river nutrient loads and represent inputs (fertilizer, manure, deposition, wastewater, N‐fixation, and weathering) minus outputs (nutrient uptake and removal in harvest, and N emissions). Here, we quantified annual changes in nitrogen (N) and phosphorus (P) river loads and nutrient balances at the MR Outlet and documented that the river load response to watershed nutrient balances shifted between 1975 and 2017. Annual nutrient balances and river loads were positively correlated between 1975 and 1985, but after, a disconnect between both the N and P balances and river loads emerged, and the subsequent river load patterns were different for N versus P. We evaluated the relative impacts of legacy nutrients and other latent factors, for which data were not available, on river nutrient load trends. Our analysis showed that in the case of N, latent factors were potentially just as important in explaining changes in river nutrient loads over time as N balances, and in the case of P, they were even more important. We hypothesized that these factors included implementation of best management practices, changes in watershed buffering capacity, the effects of tile drainage, or increased precipitation. Our analytical approach shows promise for the investigation of drivers of water quality trends that are not well‐represented in typical national scale geospatial datasets.
Terrestrial connectivity, upstream aquatic history and seasonality shape bacterial community assembly within a large boreal aquatic network
Authors: Stadler Masumi , del Giorgio Paul A
Published: November 2021

During transit from soils to the ocean, microbial communities are modified and re-assembled, generating complex patterns of ecological succession. The potential effect of upstream assembly on downstream microbial community composition is seldom considered within aquatic networks. Here, we reconstructed the microbial succession along a land-freshwater-estuary continuum within La Romaine river watershed in Northeastern Canada. We captured hydrological seasonality and differentiated the total and reactive community by sequencing both 16 S rRNA genes and transcripts. By examining how DNA- and RNA-based assemblages diverge and converge along the continuum, we inferred temporal shifts in the relative importance of assembly processes, with mass effects dominant in spring, and species selection becoming stronger in summer. The location of strongest selection within the network differed between seasons, suggesting that selection hotspots shift depending on hydrological conditions. The unreactive fraction (no/minor RNA contribution) was composed of taxa with diverse potential origins along the whole aquatic network, while the majority of the reactive pool (major RNA contribution) could be traced to soil/soilwater-derived taxa, which were distributed along the entire rank-abundance curve. Overall, our findings highlight the importance of considering upstream history, hydrological seasonality and the reactive microbial fraction to fully understand microbial community assembly on a network scale.
A medullary centre for lapping in mice
Authors: Dempsey Bowen , Sungeelee Selvee , Bokiniec Phillip , Chettouh Zoubida , Diem Séverine , Autran Sandra , Harrell Evan R. , Poulet James F. A. , Birchmeier Carmen , Carey Harry , Genovesio Auguste , McMullan Simon , Goridis Christo , Fortin Gilles , Brunet Jean-François
Published: November 2021

It has long been known that orofacial movements for feeding can be triggered, coordinated, and often rhythmically organized at the level of the brainstem, without input from higher centers. We uncover two nuclei that can organize the movements for ingesting fluids in mice. These neuronal groups, IRtPhox2b and Peri5Atoh1, are marked by expression of the pan-autonomic homeobox gene Phox2b and are located, respectively, in the intermediate reticular formation of the medulla and around the motor nucleus of the trigeminal nerve. They are premotor to all jaw-opening and tongue muscles. Stimulation of either, in awake animals, opens the jaw, while IRtPhox2b alone also protracts the tongue. Moreover, stationary stimulation of IRtPhox2b entrains a rhythmic alternation of tongue protraction and retraction, synchronized with jaw opening and closing, that mimics lapping. Finally, fiber photometric recordings show that IRtPhox2b is active during volitional lapping. Our study identifies one of the subcortical nuclei underpinning a stereotyped feeding behavior.
Polluted white dwarfs reveal exotic mantle rock types on exoplanets in our solar neighborhood
Authors: Putirka Keith D. , Xu Siyi
Published: November 2021

Prior studies have hypothesized that some polluted white dwarfs record continent-like granitic crust—which is abundant on Earth and perhaps uniquely indicative of plate tectonics. But these inferences derive from only a few elements, none of which define rock type. We thus present the first estimates of rock types on exoplanets that once orbited polluted white dwarfs—stars whose atmospheric compositions record the infall of formerly orbiting planetary objects—examining cases where Mg, Si, Ca and Fe are measured with precision. We find no evidence for continental crust, or other crust types, even after correcting for core formation. However, the silicate mantles of such exoplanets are discernable: one case is Earth like, but most are exotic in composition and mineralogy. Because these exoplanets exceed the compositional spread of >4,000 nearby main sequence stars, their unique silicate compositions are unlikely to reflect variations in parent star compositions. Instead, polluted white dwarfs reveal greater planetary variety in our solar neighborhood than currently appreciated, with consequently unique planetary accretion and differentiation paths that have no direct counterparts in our Solar System. These require new rock classification schemes, for quartz + orthopyroxene and periclase + olivine assemblages, which are proposed here.
Volumetric extrusive rates of silicic supereruptions from the Afro-Arabian large igneous province
Authors: Thines Jennifer E. , Ukstins Ingrid A. , Wall Corey , Schmitz Mark
Published: November 2021

The main phase of silicic volcanism from the Afro-Arabian large igneous province preserves some of the largest volcanic eruptions on Earth, with six units totaling >8,600 km3 dense rock equivalent (DRE). The large volumes of rapidly emplaced individual eruptions present a case study for examining the tempo of voluminous silicic magma generation and emplacement. Here were report high-precision 206Pb/238U zircon ages and show that the largest sequentially dated eruptions occurred within 48 ± 34 kyr (29.755 ± 0.023 Ma to 29.707 ± 0.025 Ma), yielding the highest known long-term volumetric extrusive rate of silicic volcanism on Earth. While these are the largest known sequential silicic supereruptions, they did not cause major global environmental change. We also provide a robust tie-point for calibration of the geomagnetic polarity timescale by integrating 40Ar/39Ar data with our 206Pb/238U ages to yield new constraints on the duration of the C11n.1r Subchron.
Potent SARS-CoV-2 neutralizing antibodies with protective efficacy against newly emerged mutational variants
Authors: Li Tingting , Han Xiaojian , Gu Chenjian , Guo Hangtian , Zhang Huajun , Wang Yingming , Hu Chao , Wang Kai , Liu Fengjiang , Luo Feiyang , Zhang Yanan , Hu Jie , Wang Wang , Li Shenglong , Hao Yanan , Shen Meiying , Huang Jingjing , Long Yingyi , Song Shuyi , Wu Ruixin , Mu Song , Chen Qian , Gao Fengxia , Wang Jianwei , Long Shunhua , Li Luo , Wu Yang , Gao Yan , Xu Wei , Cai Xia , Qu Di , Zhang Zherui , Zhang Hongqing , Li Na , Gao Qingzhu , Zhang Guiji , He Changlong , Wang Wei , Ji Xiaoyun , Tang Ni , Yuan Zhenghong , Xie Youhua , Yang Haitao , Zhang Bo , Huang Ailong , Jin Aishun
Published: November 2021

Accumulating mutations in the SARS-CoV-2 Spike (S) protein can increase the possibility of immune escape, challenging the present COVID-19 prophylaxis and clinical interventions. Here, 3 receptor binding domain (RBD) specific monoclonal antibodies (mAbs), 58G6, 510A5 and 13G9, with high neutralizing potency blocking authentic SARS-CoV-2 virus display remarkable efficacy against authentic B.1.351 virus. Surprisingly, structural analysis has revealed that 58G6 and 13G9 both recognize the steric region S470–495 on the RBD, overlapping the E484K mutation presented in B.1.351. Also, 58G6 directly binds to another region S450–458 in the RBD. Significantly, 58G6 and 510A5 both demonstrate prophylactic efficacy against authentic SARS-CoV-2 and B.1.351 viruses in the transgenic mice expressing human ACE2 (hACE2), protecting weight loss and reducing virus loads. Together, we have evidenced 2 potent neutralizing Abs with unique mechanism targeting authentic SARS-CoV-2 mutants, which can be promising candidates to fulfill the urgent needs for the prolonged COVID-19 pandemic.
A previously unrecognized membrane protein in the Rhodobacter sphaeroides LH1-RC photocomplex
Authors: Tani Kazutoshi , Nagashima Kenji V. P. , Kanno Ryo , Kawamura Saki , Kikuchi Riku , Hall Malgorzata , Yu Long-Jiang , Kimura Yukihiro , Madigan Michael T. , Mizoguchi Akira , Humbel Bruno M. , Wang-Otomo Zheng-Yu
Published: November 2021

Rhodobacter (Rba.) sphaeroides is the most widely used model organism in bacterial photosynthesis. The light-harvesting-reaction center (LH1-RC) core complex of this purple phototroph is characterized by the co-existence of monomeric and dimeric forms, the presence of the protein PufX, and approximately two carotenoids per LH1 αβ-polypeptides. Despite many efforts, structures of the Rba. sphaeroides LH1-RC have not been obtained at high resolutions. Here we report a cryo-EM structure of the monomeric LH1-RC from Rba. sphaeroides strain IL106 at 2.9 Å resolution. The LH1 complex forms a C-shaped structure composed of 14 αβ-polypeptides around the RC with a large ring opening. From the cryo-EM density map, a previously unrecognized integral membrane protein, referred to as protein-U, was identified. Protein-U has a U-shaped conformation near the LH1-ring opening and was annotated as a hypothetical protein in the Rba. sphaeroides genome. Deletion of protein-U resulted in a mutant strain that expressed a much-reduced amount of the dimeric LH1-RC, indicating an important role for protein-U in dimerization of the LH1-RC complex. PufX was located opposite protein-U on the LH1-ring opening, and both its position and conformation differed from that of previous reports of dimeric LH1-RC structures obtained at low-resolution. Twenty-six molecules of the carotenoid spheroidene arranged in two distinct configurations were resolved in the Rba. sphaeroides LH1 and were positioned within the complex to block its channels. Our findings offer an exciting new view of the core photocomplex of Rba. sphaeroides and the connections between structure and function in bacterial photocomplexes in general.
Two distinct superconducting states controlled by orientations of local wrinkles in LiFeAs
Authors: Cao Lu , Liu Wenyao , Li Geng , Dai Guangyang , Zheng Qi , Wang Yuxin , Jiang Kun , Zhu Shiyu , Huang Li , Kong Lingyuan , Yang Fazhi , Wang Xiancheng , Zhou Wu , Lin Xiao , Hu Jiangping , Jin Changqing , Ding Hong , Gao Hong-Jun
Published: November 2021

For iron-based superconductors, the phase diagrams under pressure or strain exhibit emergent phenomena between unconventional superconductivity and other electronic orders, varying in different systems. As a stoichiometric superconductor, LiFeAs has no structure phase transitions or entangled electronic states, which manifests an ideal platform to explore the pressure or strain effect on unconventional superconductivity. Here, we observe two types of superconducting states controlled by orientations of local wrinkles on the surface of LiFeAs. Using scanning tunneling microscopy/spectroscopy, we find type-I wrinkles enlarge the superconducting gaps and enhance the transition temperature, whereas type-II wrinkles significantly suppress the superconducting gaps. The vortices on wrinkles show a C2 symmetry, indicating the strain effects on the wrinkles. By statistics, we find that the two types of wrinkles are categorized by their orientations. Our results demonstrate that the local strain effect with different directions can tune the superconducting order parameter of LiFeAs very differently, suggesting that the band shifting induced by directional pressure may play an important role in iron-based superconductivity.
N1-methyladenosine methylation in tRNA drives liver tumourigenesis by regulating cholesterol metabolism
Authors: Wang Yanying , Wang Jing , Li Xiaoyu , Xiong Xushen , Wang Jianyi , Zhou Ziheng , Zhu Xiaoxiao , Gu Yang , Dominissini Dan , He Lei , Tian Yong , Yi Chengqi , Fan Zusen
Published: November 2021

Hepatocellular carcinoma (HCC) accounts for the majority of primary liver cancers and is characterized by high recurrence and heterogeneity, yet its mechanism is not well understood. Here we show that N1-methyladenosine methylation (m1A) in tRNA is remarkably elevated in hepatocellular carcinoma (HCC) patient tumour tissues. Moreover, m1A methylation signals are increased in liver cancer stem cells (CSCs) and are negatively correlated with HCC patient survival. TRMT6 and TRMT61A, forming m1A methyltransferase complex, are highly expressed in advanced HCC tumours and are negatively correlated with HCC survival. TRMT6/TRMT61A-mediated m1A methylation is required for liver tumourigenesis. Mechanistically, TRMT6/TRMT61A elevates the m1A methylation in a subset of tRNA to increase PPARδ translation, which in turn triggers cholesterol synthesis to activate Hedgehog signaling, eventually driving self-renewal of liver CSCs and tumourigenesis. Finally, we identify a potent inhibitor against TRMT6/TRMT61A complex that exerts effective therapeutic effect on liver cancer.
Antimicrobial and cytotoxic capacity of pyroligneous extracts films of Eucalyptus grandis and chitosan for oral applications
Authors: de Souza Juliana Leitzke Santos , Alves Tomaz , Camerini Laísa , Nedel Fernanda , Campos Angela Diniz , Lund Rafael Guerra
Published: November 2021

Chitosan films containing distilled pyroligneous extracts of Eucalyptus grandis (DPEC), characterized and developed by Brazilian Agricultural Research Corporation—Embrapa Temperate Agriculture (EMBRAPA-CPACT), were evaluated for antimicrobial activity against Candida albicans, Streptococcus mutans, and Lactobacillus acidophilus by direct contact test. Further, their capacity for the prevention of teeth enamel demineralization and cytotoxicity in vitro were also determined. The natural polymers were tested at different concentrations (1500–7500 µg mL−1) and the formulation of an experimental fluoride varnish with antimicrobial activity was evaluated by direct contact test, whereas cytotoxicity was analyzed through the colorimetric MTT assay. Preliminary data showed no statistically significant differences in cytotoxicity to NIH/3T3 cell line when DPEC is compared to the control group. On the other hand, the antimicrobial capacity and demineralization effects were found between the test groups at the different concentrations tested. Chitosan films containing distilled pyroligneous extracts of E. grandis may be an effective control strategy to prevent biofilm formation related to dental caries when applied as a protective varnish. They may inhibit the colonization of oral microorganisms and possibly control dental caries through a decrease in pH and impairment of enamel demineralization.
Unveiling microbial preservation under hyperacidic and oxidizing conditions in the Oligocene Rio Tinto deposit
Authors: Fernández-Remolar David C. , Carrizo Daniel , Harir Mourad , Huang Ting , Amils Ricardo , Schmitt-Kopplin Philippe , Sánchez-García Laura , Gomez-Ortiz David , Malmberg Per
Published: November 2021

The preservation of biosignatures on Mars is largely associated with extensive deposits of clays formed under mild early Noachian conditions (> 3.9 Ga). They were followed by widespread precipitation of acidic sulfates considered adverse for biomolecule preservation. In this paper, an exhaustive mass spectrometry investigation of ferric subsurface materials in the Rio Tinto gossan deposit (~ 25 Ma) provides evidence of well-preserved molecular biosignatures under oxidative and acidic conditions. Time of flight secondary ion mass spectrometry (ToF–SIMS) analysis shows a direct association between physical-templating biological structures and molecular biosignatures. This relation implies that the quality of molecular preservation is exceptional and provides information on microbial life formerly operating in the shallow regions of the Rio Tinto subsurface. Consequently, low-pH oxidative environments on Mars could also record molecular information about ancient life in the same way as the Noachian clay-rich deposits.
The effect of age and sex on the expression of GABA signaling components in the human hippocampus and entorhinal cortex
Authors: Ethiraj Jayarjun , Palpagama Thulani Hansika , Turner Clinton , van der Werf Bert , Waldvogel Henry John , Faull Richard Lewis Maxwell , Kwakowsky Andrea
Published: November 2021

Gamma-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the nervous system. The GABA signaling system in the brain is comprised of GABA synthesizing enzymes, transporters, GABAA and GABAB receptors (GABAAR and GABABR). Alterations in the expression of these signaling components have been observed in several brain regions throughout aging and between sexes in various animal models. The hippocampus is the memory centre of the brain and is impaired in several age-related disorders. It is composed of two main regions: the Cornu Ammonis (CA1-4) and the Dentate Gyrus (DG), which are interconnected with the Entorhinal Cortex (ECx). The age- and sex-specific changes of GABA signaling components in these regions of the human brain have not been examined. This study is the first to determine the effect of age and sex on the expression of GABA signaling components-GABAAR α1,2,3,5, β1-3, γ2, GABABR R1 and R2 subunits and the GABA synthesizing enzymes GAD 65/67-in the ECx, and the CA1 and DG regions of the human hippocampus using Western blotting. No significant differences were found in GABAAR α1,2,3,5, β1-3, γ2, GABABR R1 and R2 subunit and GAD65/76 expression levels in the ECx, CA1 and DG regions between the younger and older age groups for both sexes. However, we observed a significant negative correlation between age and GABAAR α1subunit level in the CA1 region for females; significant negative correlation between age and GABAAR β1, β3 and γ2 subunit expression in the DG region for males. In females a significant positive correlation was found between age and GABAAR γ2 subunit expression in the ECx and GABABR R2 subunit expression in the CA1 region. The results indicate that age and sex do not affect the expression of GAD 65/67. In conclusion, our results show age- and sex-related GABAA/BR subunit alterations in the ECx and hippocampus that might significantly influence GABAergic neurotransmission and underlie disease susceptibility and progression.
Circulation patterns of human seasonal Influenza A viruses in Chile before H1N1pdm09 pandemic
Authors: Mena Juan , Tapia Rodrigo , Verdugo Claudio , Avendaño Luis , Parra-Castro Paulina , Medina Rafael A. , Barriga Gonzalo , Neira Víctor
Published: November 2021

Understanding the diversity and circulation dynamics of seasonal influenza viruses is key to public health decision-making. The limited genetic information of pre-pandemic seasonal IAVs in Chile has made it difficult to accurately reconstruct the phylogenetic relationships of these viruses within the country. The objective of this study was to determine the genetic diversity of pre-pandemic human seasonal IAVs in Chile. We sequenced the complete genome of 42 historic IAV obtained between 1996 and 2007. The phylogeny was determined using HA sequences and complemented using other segments. Time-scale phylogenetic analyses revealed that the diversity of pre-pandemic human seasonal IAVs in Chile was influenced by continuous introductions of new A/H1N1 and A/H3N2 lineages and constant viral exchange between Chile and other countries every year. These results provide important knowledge about genetic diversity and evolutionary patterns of pre-pandemic human seasonal IAVs in Chile, which can help design optimal surveillance systems and prevention strategies. However, future studies with current sequences should be conducted.
β2-adrenergic receptor regulates ER-mitochondria contacts
Authors: Lim Youngshin , Cho Il-Taeg , Rennke Helmut G. , Cho Ginam
Published: November 2021

Interactions between the endoplasmic reticulum (ER) and mitochondria (Mito) are crucial for many cellular functions, and their interaction levels change dynamically depending on the cellular environment. Little is known about how the interactions between these organelles are regulated within the cell. Here we screened a compound library to identify chemical modulators for ER-Mito contacts in HEK293T cells. Multiple agonists of G-protein coupled receptors (GPCRs), beta-adrenergic receptors (β-ARs) in particular, scored in this screen. Analyses in multiple orthogonal assays validated that β2-AR activation promotes physical and functional interactions between the two organelles. Furthermore, we have elucidated potential downstream effectors mediating β2-AR-induced ER-Mito contacts. Together our study identifies β2-AR signaling as an important regulatory pathway for ER-Mito coupling and highlights the role of these contacts in responding to physiological demands or stresses.
Distance between the center of the FAZ measured automatically and the highest foveal bulge using OCT-angiography in elderly healthy eyes
Authors: Shoji Takuhei , Ishii Hirokazu , Kanno Junji , Sasaki Takanori , Yoshikawa Yuji , Ibuki Hisashi , Shinoda Kei
Published: November 2021

The center of the fovea, termed the foveola, is the area of highest visual acuity, has the highest density of cone photoreceptors. We investigated the distance between the automatically-determined center of the foveal avascular zone (FAZ) and the manually-determined highest foveal bulge (FB) point using single swept-source optical coherence tomography angiography (OCTA) instrument. This cross-sectional study included 49 eyes of 49 individuals (34 women and 15 men; median age: 68 years) with no history of ocular disorders. The FAZ in the superficial capillary plexus was automatically determined using the Kanno–Saitama macro method, and the center of the FAZ was automatically determined using ellipse approximation. Another candidate foveal center, the highest FB point, was determined manually on the serial cross-sectional B-scan images. As a result, the foveal center was manually identified as the highest FB point on B-scan OCTA images. The center of the FAZ was more likely to be located inferior to the highest FB point (p = 0.031). In participants with a total (linear) distance of more than 50 μm between the center of the FAZ and the highest FB point, the displacement was significantly more in the horizontal direction than in the vertical direction (p = 0.017). These results can be applicable to further studies regarding the spatial relationships between the center of the FAZ and the highest FB point in various macular diseases or previously-treated eyes.
The immune checkpoint VISTA exhibits high expression levels in human gliomas and associates with a poor prognosis
Authors: Ghouzlani Amina , Lakhdar Abdelhakim , Rafii Soumaya , Karkouri Mehdi , Badou Abdallah
Published: November 2021

In human gliomas, anti-tumor T cell responses are inhibited through induction of local and systemic immunosuppression. Immune checkpoint blockade is proving to be a success in several types of cancers. However, many studies reported that the treatment of glioblastoma patients with anti-CTLA-4 or anti-PD-1 has no survival benefit compared to standard chemotherapy. This study aimed to investigate the expression and role of VISTA, a newly described immune checkpoint regulator, in human gliomas. mRNA expression was assessed in a total of 87 samples from glioma patients. 57 glioma tissues were taken at different grades. 20 peripheral blood mononuclear cells (PBMC) samples were taken before surgery and ten after surgery, all from the same set of patients. As for the control, ten specimens of PBMC were taken from healthy donors. Protein expression using immunohistochemistry was performed for 30 patients. The Cancer Genome Atlas (TCGA) data set, was also used to investigate VISTA expression through analysis of RNA-seq data of 667 glioma patients. In the Moroccan cohort, VISTA gene expression was significantly upregulated in glioma tissues related to PBMC of healthy donors. This high expression was specific to patient tissues since VISTA expression in PBMC was low when assessed either before or after surgery. Besides, VISTA exhibited higher expression levels in grade III/IV relative to grade I/II glioma patients. Interestingly, VISTA correlated positively with PD-1 expression. PD-1 also showed elevated expressions in higher glioma grades. The TCGA cohort corroborated these observations. Indeed, VISTA was also found to be strongly expressed in high grades. It was positively correlated with other critical immune checkpoints. Finally, increased VISTA transcript levels were associated with weak overall survival of glioma patients. Our study highlighted a correlation between high levels of VISTA expression and poor prognosis in glioma patients. VISTA might be involved in glioma progression and could be considered as a possible new therapeutic target, especially in advanced gliomas.
Learning exceptions to the rule in human and model via hippocampal encoding
Authors: Heffernan Emily M. , Schlichting Margaret L. , Mack Michael L.
Published: November 2021

Category learning helps us process the influx of information we experience daily. A common category structure is “rule-plus-exceptions,” in which most items follow a general rule, but exceptions violate this rule. People are worse at learning to categorize exceptions than rule-following items, but improved exception categorization has been positively associated with hippocampal function. In light of model-based predictions that the nature of existing memories of related experiences impacts memory formation, here we use behavioural and computational modelling data to explore how learning sequence impacts performance in rule-plus-exception categorization. Our behavioural results indicate that exception categorization accuracy improves when exceptions are introduced later in learning, after exposure to rule-followers. To explore whether hippocampal learning systems also benefit from this manipulation, we simulate our task using a computational model of hippocampus. The model successful replicates our behavioural findings related to exception learning, and representational similarity analysis of the model’s hidden layers suggests that model representations are impacted by trial sequence: delaying the introduction of an exception shifts its representation closer to its own category members. Our results provide novel computational evidence of how hippocampal learning systems can be targeted by learning sequence and bolster extant evidence of hippocampus’s role in category learning.
The role of interplate locking on the seismic reactivation of upper plate faults on the subduction margin of northern Chile
Authors: González Gabriel , Pasten-Araya Francisco , Victor Pia , González Yerko , Valenzuela Jordán , Shrivastava Mahesh
Published: November 2021

Quaternary deformation in the northern Chile forearc is controlled by trench parallel shortening along reactivated Mesozoic faults. Dextral strikes-slip is expressed in NW–SE striking faults of the Atacama Fault System, and reverse displacement dominates in E–W faults. This deformation results of the convergence in a concave-seaward continental margin. On September 11th, 2020, a Mw6.3 earthquake and its subsequent aftershocks took place in the coastal region of northern Chile, revealing the reactivation of the deepest segment of a WNW–ESE striking upper plate fault. The reactivation of this fault occurred after the Mw8.1 Iquique earthquake, and it seems to be connected to a N–S interplate locking segmentation of the plate margin, which is clearly shown by the locking pattern before the Iquique earthquake. This poses the question of how heterogeneous locking influences upper plate seismicity and how it relates to trench-parallel shortening.
Risk assessment and prognostic analysis of patients with splenic infarction in emergency department: a multicenter retrospective study
Authors: Yen Chieh-Ching , Wang Chih-Kai , Chen Shou-Yen , Gao Shi-Ying , Lo Hsiang-Yun , Ng Chip-Jin , Chaou Chung-Hsien
Published: November 2021

Splenic infarction is a thromboembolic disease that is frequently missed in acute settings. Previous reviews were rarely presented from a clinical perspective. We aimed to evaluate the clinical characteristics, risk factors with diagnostic value, and prognostic factors using large cohort data and a matched case–control study method. A retrospective medical record review of six hospitals in Taiwan from January 1, 2005, to August 31, 2020, was conducted. All patients who underwent contrast CT with confirmed the diagnosis of splenic infarction were included. Their characteristics were presented and compared to a matched control group with similar presenting characteristics. Prognostic factors were also analyzed. A total of 130 cases were included, two-thirds of whom presented with abdominal pain. Atrial fibrillation was the most common associated predisposing condition, followed by hematologic disease. A higher proportion of tachycardia, positive qSOFA score, history of hypertension or atrial fibrillation, leukocytosis, and thrombocytopenia were found in splenic infarction patients compared to their counterparts. An underlying etiology of infective endocarditis was associated with a higher proportion of ICU admission. Splenic infarction patients often presented with left upper abdominal pain and tachycardia. A history of hypertension, atrial fibrillation, a laboratory result of leukocytosis or thrombocytopenia may provide a clue for clinicians to include splenic infarction in the differential list. Among the patients diagnosed with splenic infarction, those with an underlying etiology of infectious endocarditis may be prone to deterioration or ICU admission.
Development of accurate temperature regulation culture system with metallic culture vessel demonstrates different thermal cytotoxicity in cancer and normal cells
Authors: Imashiro Chikahiro , Takeshita Haruka , Morikura Takashi , Miyata Shogo , Takemura Kenjiro , Komotori Jun
Published: November 2021

Hyperthermia has been studied as a noninvasive cancer treatment. Cancer cells show stronger thermal cytotoxicity than normal cells, which is exploited in hyperthermia. However, the absence of methods evaluating the thermal cytotoxicity in cells prevents the development of hyperthermia. To investigate the thermal cytotoxicity, culture temperature should be regulated. We, thus, developed a culture system regulating culture temperature immediately and accurately by employing metallic culture vessels. Michigan Cancer Foundation-7 cells and normal human dermal fibroblasts were used for models of cancer and normal cells. The findings showed cancer cells showed stronger thermal cytotoxicity than normal cells, which is quantitatively different from previous reports. This difference might be due to regulated culture temperature. The thermal stimulus condition (43 °C/30 min) was, further, focused for assays. The mRNA expression involving apoptosis changed dramatically in cancer cells, indicating the strong apoptotic trend. In contrast, the mRNA expression of heat shock protein (HSP) of normal cells upon the thermal stimulus was stronger than cancer cells. Furthermore, exclusively in normal cells, HSP localization to nucleus was confirmed. These movement of HSP confer thermotolerance to cells, which is consistent with the different thermal cytotoxicity between cancer and normal cells. In summary, our developed system can be used to develop hyperthermia treatment.
Impact of type of reconstructed residence on social participation and mental health of population displaced by disasters
Authors: Suzuki Tomomi , Akaishi Tetsuya , Nemoto Harumi , Utsumi Yusuke , Seto Moe , Usukura Hitomi , Kunii Yasuto , Sugawara Yumi , Nakaya Naoki , Nakamura Tomohiro , Tsuchiya Naho , Narita Akira , Kogure Mana , Hozawa Atsushi , Tsuji Ichiro , Ishii Tadashi , Tomita Hiroaki
Published: November 2021

After disasters, people are often forced to reconstruct or move to new residences. This study aimed to reveal the association between the types of reconstructed residences and psychosocial or psychiatric conditions among the population. A total of 1071 adult residents in a coastal town, whose houses were destroyed by the tsunami caused by the Great East Japan Earthquake, enrolled in the study five years after the disaster. The type of reconstructed post-disaster residences (reconstructed on the same site/disaster-recovery public condominium/mass-translocation to higher ground/privately moving to remote areas) and the current psychosocial indicators were investigated. The results revealed that individuals living in public condominiums showed significantly worse scores on the Lubben Social Network Scale-6 (p < 0.0001) and the Center for Epidemiologic Studies Depression Scale (p < 0.0001), and slightly worse scores on the Kessler Psychological Distress Scale (p = 0.035) and the Impact of Event Scale-Revised (p = 0.028). Lower psychosocial indicator scores in the public condominium group were more remarkable in younger adults aged < 65 years. Insomnia evaluated using the Athens Insomnia Scale was not different among the four residential types. In summary, residents moving into disaster-recovery public condominiums are likely to have less social interaction, be more depressed, and may need additional interventions.
Microinjection of pruritogens in NGF-sensitized human skin
Authors: Solinski Hans Jürgen , Rukwied Roman , Schmelz Martin
Published: November 2021

Single intradermal injections of nerve growth factor (NGF) evoke prolonged but temporally distinct sensitization patterns to somatosensory stimuli. Focal administration of the non-histaminergic pruritogen cowhage but not histamine resulted in elevated itch at day 21 after NGF administration. Here, we injected bovine adrenal medulla peptide 8–22 (BAM8–22), β-alanine (β-ALA) and endothelin-1 (ET-1) into NGF-treated skin of 11 healthy volunteers and investigated the corresponding itch/pain and flare reactions. β-ALA was the weakest pruritogen, while BAM8–22 and ET-1 were equally potent as histamine. NGF did not sensitize itch or flare reactions induced by any compound, but injection and evoked pain were increased at day 21 and 49. The involvement of histamine H1 receptors in itch was explored in eight subjects after oral cetirizine. ET-1-induced itch and flare were significantly reduced. BAM8–22 and β-ALA itch were not affected, but flare responses after BAM8–22 reduced by 50%. The results indicate that a single NGF injection does not sensitize for experimentally induced itch but increases pain upon pruritogen injection. In healthy humans, pruritic and algetic processing appear differentially regulated by NGF. However, in patients suffering chronic itch, prolonged elevation of NGF-levels under inflammatory conditions may contribute to elevated itch.
Combining genetic risk score with artificial neural network to predict the efficacy of folic acid therapy to hyperhomocysteinemia
Authors: Chen Xiaorui , Huang Xiaowen , Jie Diao , Zheng Caifang , Wang Xiliang , Zhang Bowen , Shao Weihao , Wang Gaili , Zhang Weidong
Published: November 2021

Artificial neural network (ANN) is the main tool to dig data and was inspired by the human brain and nervous system. Several studies clarified its application in medicine. However, none has applied ANN to predict the efficacy of folic acid treatment to Hyperhomocysteinemia (HHcy). The efficacy has been proved to associate with both genetic and environmental factors while previous studies just focused on the latter one. The explained variance genetic risk score (EV-GRS) had better power and could represent the effect of genetic architectures. Our aim was to add EV-GRS into environmental factors to establish ANN to predict the efficacy of folic acid therapy to HHcy. We performed the prospective cohort research enrolling 638 HHcy patients. The multilayer perception algorithm was applied to construct ANN. To evaluate the effect of ANN, we also established logistic regression (LR) model to compare with ANN. According to our results, EV-GRS was statistically associated with the efficacy no matter analyzed as a continuous variable (OR = 3.301, 95%CI 1.954–5.576, P < 0.001) or category variable (OR = 3.870, 95%CI 2.092–7.159, P < 0.001). In our ANN model, the accuracy was 84.78%, the Youden’s index was 0.7073 and the AUC was 0.938. These indexes above indicated higher power. When compared with LR, the AUC, accuracy, and Youden’s index of the ANN model (84.78%, 0.938, 0.7073) were all slightly higher than the LR model (83.33% 0.910, 0.6687). Therefore, clinical application of the ANN model may be able to better predict the folic acid efficacy to HHcy than the traditional LR model. When testing two models in the validation set, we got the same conclusion. This study appears to be the first one to establish the ANN model which added EV-GRS into environmental factors to predict the efficacy of folic acid to HHcy. This model would be able to offer clinicians a new method to make decisions and individual therapeutic plans.
Association analysis of KIR/HLA genotype with liver cirrhosis, hepatocellular carcinoma, and NUC freedom in chronic hepatitis B patients
Authors: Joshita Satoru , Ota Masao , Kobayashi Hiroyuki , Wakabayashi Shun-ichi , Yamashita Yuki , Sugiura Ayumi , Yamazaki Tomoo , Tanaka Eiji , Umemura Takeji
Published: November 2021

Natural killer cells are modulated through the binding of killer cell immunoglobulin-like receptors (KIRs) with human leukocyte antigen (HLA) class I ligands. This study investigated the association of KIR/HLA pairs with progression to liver cirrhosis, hepatocellular carcinoma (HCC) development, and nucleot(s)ide (NUC) treatment freedom in hepatitis B virus (HBV) infection. KIR, HLA-Bw, and HLA-C were genotyped in 280 Japanese HBV patients for clinical comparisons. No significant associations of KIR/HLA pairs were detected in terms of liver cirrhosis development. The KIR2DS3 positive rate was significantly higher in patients with HCC (n = 39) than in those without (n = 241) [30.8% vs. 14.9%, odds ratio (OR) 2.53, P = 0.015]. The KIR3DL1/HLA-Bw4 pair rate was significantly lower in the NUC freedom group (n = 20) than in the NUC continue group (n = 114) (25.0% vs. 52.6%, OR 0.30, P = 0.042). In conclusion, this study indicated remarkable associations of KIR/HLA with HCC development (KIR2DS3) and freedom from NUC therapy (KIR3DL1/HLA-Bw4) in HBV patients, although the number of cases was insufficient for statistical purposes. Additional multi-center analyses of larger groups are needed to clarify whether KIR/HLA pairs play a role in HBV patient status.