bluuebunny/crossref_metadata_2025 huggingface dataset:
Carbon and Nitrogen Dynamics in Mexican Management Forest: Simulation of Biomass Harvesting and C and N Amendments
Authors: Ordoñez Maria-Cristina , Galicia Leopoldo , Valladares-Samperio Karla
Published: December 2021

Sustainable silvicultural management requires the maintenance of long-term ecosystem processes. We used the CENTURY model to simulate the impact of wood extraction and organic amendments on aboveground biomass, carbon (C) storage, and the availability of nitrogen (N) in the two dominant silvicultural methods in Mexico: the silvicultural development method (SDM) and irregular forest management (IFM). The values of the mean absolute percentage error for the SDM and IFM were 2.1% and 3.3% for C in aboveground biomass, 5.7% and 5.0% for soil organic carbon (SOC), and 14.9% and 21.6% for N, respectively. Simulation for the SDM (1967–2068) suggested a reduction of ~7% in C in soil, microbial biomass, and litter, 9% in aboveground biomass C, and ~20% in the mineral N available. For IFM, the simulation (2009–2019) suggested a reduction of 14% in the accumulation of aboveground biomass and 13% in the mineral N available. Simulation of the adoption of management practices suggested that N mineral availability would increase by 2%–3% without drastically reducing the SOC, improving aboveground biomass production by ~7%, in each management system.

Study Implications

In Mexico, current silvicultural management is causing alterations in the biological and chemical processes of the soil, but the future impacts on the production of forest wood and loss of fertility cannot be estimated by direct measurements. We simulated two silvicultural management alternatives with two rotation cycles and measured the response in terms of SOC, nitrogen availability, and aboveground biomass. The model shows that improving forest residue management by adding organic amendments to the soil would counteract changes in soil microbial activity, nitrogen availability, SOC, and aboveground biomass in the future. Managers should consider this information to reorient current crop residue management to achieve the objectives and the sustainability of forest management in Mexican temperate forests.
P-wave anisotropic tomography of NE China: insight into lithospheric deformation, mantle dynamics and intraplate volcanism
Authors: Jia Ruo , Zhao Dapeng , Wu Jianping
Published: December 2021

We determine robust 3-D P-wave anisotropic tomography of the crust and upper mantle beneath NE China using high-quality traveltime data of local earthquakes and teleseismic events recorded at 334 network and portable stations. In the upper crust, nearly E-W fast-velocity directions (FVDs) of azimuthal anisotropy are revealed in the central Songliao basin, which is surrounded by circular-shaped FVDs along the basin edges. The E-W FVDs may reflect microcracks or fractures in the upper crust, which are aligned under the control of regional tectonic stress. In the lower crust, low-velocity (low-V) anomalies with NE-SW FVDs exist along the Tanlu fault zone, which may reflect NE-SW trending ductile deformation or viscous flow along the fault zone. The FVDs are mainly NNW-SSE to N-S in the uppermost mantle beneath most of the study region, which may reflect fossil deformation of the mantle lithosphere caused by the Palaeo-Pacific plate subduction. High-velocity anomalies with NE-SW FVDs are revealed at ∼100 km depth directly beneath the Great XingAn Mountain, which may reflect an old lithospheric remnant. In the deep upper mantle, the FVDs are mostly NW-SE, consistent with SKS splitting measurements, which may be closely related to the intermittently retreating stagnant Pacific slab beneath East Asia. Under the Changbai and other intraplate volcanoes in NE China, prominent low-V anomalies exist in the big mantle wedge (BMW) above the slab in the mantle transition zone, suggesting that these volcanoes are caused by hot and wet upwelling flows in the BMW closely associated with the deep subduction and dehydration of the western Pacific plate.
Learning curve of uniportal video-assisted thoracoscopic lobectomy: an analysis of the proficiency of 538 cases from a single centre
Authors: Li Wen-Hao , Cheng Hua , Gan Xiang-Feng , Li Xiao-Jian , Wang Xiao-Jin , Wu Xiang-Wen , Zhong Hong-Cheng , Wu Tian-Chi , Huo Wen-Wen , Ju Shao-Long , Lv Liang-Zhan , Cao Qing-Dong
Published: December 2021

OBJECTIVES

Uniportal video-assisted thoracoscopic surgery (UniVATS) is widely used as a minimally invasive thoracic operation. The goal of our study was to analyse the effect of long-term experience with the UniVATS lobectomy on the learning curve.

METHODS

The learning curves were quantitatively evaluated by the unadjusted cumulative sum, and they were segmented using joinpoint linear regression analysis. The variables were compared between subgroups using trend analysis, and linear regression analysis was applied to correlate clinical characteristics at different stages of the learning curve with the duration of the operation.

RESULTS

The learning curve for the UniVATS lobectomy can be divided into 3 phases of proficiency at ∼200–300 procedures, with a fourth phase as the number of procedures increases. The 1st–52nd, 52nd–156th, 156th–244th and 244th–538th procedures comprised the preliminary learning stage, preliminary proficiency stage, proficiency stage and advanced proficiency stage, respectively. Surgical outcomes and their variability between stages improved with increasing case numbers, with the most significant addition of an auxiliary operating port and conversions. In multivariable analysis, as stages progressed, influences other than surgical experience increased the operative time, with male and extensive pleural adhesions in the preliminary proficiency stage; male and incomplete pulmonary fissures in the proficiency stage; and male, extensive pleural adhesions and incomplete pulmonary fissures in the advanced proficiency stage.

CONCLUSIONS

As the number of procedures increases, there may be 4 different proficiency stages in the UniVATS lobectomy learning curve. The surgeon enters the fourth stage at approximately the 244th procedure. Moreover, at stage 4, the perioperative indicators tend to stabilize, and influences other than surgical experience become more significant.
From Voluntary Repatriation to Voluntary Re-Establishment: Cessation of Refugee Status under Article 1C(4) of the Refugee Convention
Authors: Pearson Esther
Published: December 2021

With refugees repatriating in increasing numbers to countries of origin affected by protracted conflict, article 1C(4) of the 1951 Convention relating to the Status of Refugees, providing for the cessation of refugee status where a refugee becomes ‘voluntarily re-established’ in his or her country of origin, is of key relevance. This article considers the application of article 1C(4) to the repatriation of refugees to countries of origin affected by protracted conflict, particularly from countries of asylum struggling with an influx of refugees. It does so in the context of the ongoing return of refugees to Syria from Lebanon and Jordan. The article analyses the interpretation of the elements of ‘voluntariness’ and ‘re-establishment’, and, on the basis of this analysis, argues that the cessation of rights and protections afforded to registered refugees in Lebanon and Jordan does not satisfy these elements. It recommends that action be taken by government and humanitarian authorities in Lebanon and Jordan to guarantee the ‘voluntariness’ of return and resettlement, and observes that durable re-establishment is unlikely to be realized by many Syrian returnees in the short term. The article also measures procedures used in the Syrian context against procedural guidance on the invocation of article 1C(4), and strongly recommends that procedures based on fairness and natural justice be implemented and complied with.
Rapid evolution of a Morgagni hernia with herniation of the left hepatic lobe: case report and review of the literature
Authors: Phillips Jacquelyn , Brigode William M , Svahn Jonathan
Published: December 2021

Morgagni hernias are a rare form of congenital diaphragmatic hernia, commonly found on cross-sectional imaging. Repair is generally performed electively for pulmonary or gastrointestinal symptoms. Our case presented acutely with gastric obstruction. Two months prior she had a small bowel obstruction and underwent computed tomography, diagnostic laparoscopy, lysis of adhesions and takedown of the falciform ligament, where a ‘groove’ to the left of the falciform was noted, but not repaired. We collected the presentation, technique, complications and results of 12 prior cases. A trans-abdominal, robotic-assisted tissue repair of the diaphragm with mesh reinforcement utilizing as few as three ports appears to be safe and effective. The robotic platform offers additional degrees of freedom, making retrosternal operating more ergonomic to the surgeon. The rapid progression of our patient suggests that repair at the time of discovery should be considered so that the serious complications can be avoided.
SkyMapper colours of Seyfert galaxies and changing-look AGN – II. Newly discovered changing-look AGN
Authors: Hon Wei Jeat , Wolf Christian , Onken Christopher A , Webster Rachel , Auchettl Katie
Published: December 2021

Changing-look active galactic nuclei (CLAGN) are AGN that change type as their broad emission lines appear or disappear, which is usually accompanied by strong flux changes in their blue featureless continuum. We search for turn-on CLAGN by selecting type-2 AGN from the spectroscopic Six-degree Field Galaxy Survey (6dFGS), whose colours, observed ∼15 yr later by the SkyMapper Southern Survey, are suggestive of type-1 AGN. Starting from 1092 type-2 AGN, we select 20 candidates for follow-up and confirm that 14 of them have changed into type-1 and are thus turn-on CLAGN; further observations reveal 11 more turn-on CLAGN. While our search was not tailored to efficiently discover turn-off CLAGN, we discover two such cases as well. The result suggests a turn-on CLAGN rate of over 3 per cent over ∼15 yr and imply a total CLAGN rate of more than ∼6 per cent over this period. Finally, we present observations of AGN that are atypical for the CLAGN phenomenology, including J1109146 – a type-1 that did not appear as an AGN at all in 6dFGS; J1406507 – the second reported changing-look narrow-line Seyfert 1; and J1340153 – a CLAGN with a change time-scale of 3 months.
Synchronous X-ray/optical quasi-periodic oscillations from the black hole LMXB MAXI J1820+070
Authors: Thomas Jessymol K , Buckley David A H , Charles Philip A , Paice John A , Potter Stephen B , Steiner James F , Lasota Jean-Pierre , Gandhi P , Tao Lian , Ma Xiang , Yang Yi-Jung , Tuo Youli , Zhang Shuang-Nan
Published: December 2021

We present high-speed optical photometry from SAAO and SALT on the black hole LMXB MAXI J1820+070  (ASSASN-18ey), some of it simultaneous with NICER, Swift, and Insight-HXMT X-ray coverage. We detect optical quasi-periodic oscillations (QPOs) that move to higher frequencies as the outburst progresses, tracking both the frequency and evolution of similar X-ray QPOs previously reported. Correlated X-ray/optical data reveal a complex pattern of lags, including an anticorrelation and a sub-second lag that evolve over the first few weeks of outburst. They also show correlated components separated by a lag equal to the QPO period roughly centered on zero lag, implying that the inter-band variability is strongly and consistently affected by these QPOs at a constant phase lag of roughly ±π. The synchronization of X-ray and optical QPOs indicates that they must be produced in regions physically very close to each other; we, thus, propose that they can be explained by a precessing jet model, based on analogies with V404 Cyg and MAXI J1348−630.
ATRX loss promotes immunosuppressive mechanisms in IDH1 mutant glioma
Authors: Hu Chengchen , Wang Kimberly , Damon Ceylan , Fu Yi , Ma Tengjiao , Kratz Lisa , Lal Bachchu , Ying Mingyao , Xia Shuli , Cahill Daniel P , Jackson Christopher M , Lim Michael , Laterra John , Li Yunqing
Published: December 2021

Background

ATRX inactivation occurs with IDH1R132H and p53 mutations in over 80% of Grades II/III astrocytomas. It is believed that ATRX loss contributes to oncogenesis by dysregulating epigenetic and telomere mechanisms but effects on anti-glioma immunity have not been explored. This paper examines how ATRX loss contributes to the malignant and immunosuppressive phenotypes of IDH1R132H/p53mut glioma cells and xenografts.

Methods

Isogenic astrocytoma cells (+/−IDH1R132H/+/−ATRXloss) were established in p53mut astrocytoma cell lines using lentivirus encoding doxycycline-inducible IDH1R132H, ATRX shRNA, or Lenti-CRISPR/Cas9 ATRX. Effects of IDH1R132H+/−ATRXloss on cell migration, growth, DNA repair, and tumorigenicity were evaluated by clonal growth, transwell and scratch assays, MTT, immunofluorence and immunoblotting assays, and xenograft growth. Effects on the expression and function of modulators of the immune microenvironment were quantified by qRT-PCR, immunoblot, T-cell function, macrophage polarization, and flow cytometry assays. Pharmacologic inhibitors were used to examine epigenetic drivers of the immunosuppressive transcriptome of IDH1R132H/p53mut/ATRXloss cells.

Results

Adding ATRX loss to the IDH1R132H/p53mut background promoted astrocytoma cell aggressiveness, induced expression of BET proteins BRD3/4 and an immune-suppressive transcriptome consisting of up-regulated immune checkpoints (e.g., PD-L1, PD-L2) and altered cytokine/chemokine profiles (e.g., IL33, CXCL8, CSF2, IL6, CXCL9). ATRX loss enhanced the capacity of IDH1R132H/p53mut cells to induce T-cell apoptosis, tumorigenic/anti-inflammatory macrophage polarization and Treg infiltration. The transcriptional and biological immune-suppressive responses to ATRX loss were enhanced by temozolomide and radiation and abrogated by pharmacologic BET inhibition.

Conclusions

ATRX loss activates a BRD-dependent immune-suppressive transcriptome and immune escape mechanism in IDH1R132H/p53mut astrocytoma cells.
Radiomics for the noninvasive prediction of the BRAF mutation status in patients with melanoma brain metastases
Authors: Meißner Anna-Katharina , Gutsche Robin , Galldiks Norbert , Kocher Martin , Jünger Stephanie T , Eich Marie-Lisa , Montesinos-Rongen Manuel , Brunn Anna , Deckert Martina , Wendl Christina , Dietmaier Wolfgang , Goldbrunner Roland , Ruge Maximilian I , Mauch Cornelia , Schmidt Nils-Ole , Proescholdt Martin , Grau Stefan , Lohmann Philipp
Published: December 2021

Background

The BRAF V600E mutation is present in approximately 50% of patients with melanoma brain metastases and an important prerequisite for response to targeted therapies, particularly BRAF inhibitors. As heterogeneity in terms of BRAF mutation status may occur in melanoma patients, a wild-type extracranial primary tumor does not necessarily rule out a targetable mutation in brain metastases using BRAF inhibitors. We evaluated the potential of MRI radiomics for a noninvasive prediction of the intracranial BRAF mutation status.

Methods

Fifty-nine patients with melanoma brain metastases from two university brain tumor centers (group 1, 45 patients; group 2, 14 patients) underwent tumor resection with subsequent genetic analysis of the intracranial BRAF mutation status. Preoperative contrast-enhanced MRI was manually segmented and analyzed. Group 1 was used for model training and validation, group 2 for model testing. After radiomics feature extraction, a test-retest analysis was performed to identify robust features prior to feature selection. Finally, the best performing radiomics model was applied to the test data. Diagnostic performances were evaluated using receiver operating characteristic (ROC) analyses.

Results

Twenty-two of 45 patients (49%) in group 1, and 8 of 14 patients (57%) in group 2 had an intracranial BRAF V600E mutation. A linear support vector machine classifier using a six-parameter radiomics signature yielded an area under the ROC curve of 0.92 (sensitivity, 83%; specificity, 88%) in the test data.

Conclusions

The developed radiomics classifier allows a noninvasive prediction of the intracranial BRAF V600E mutation status in patients with melanoma brain metastases with high diagnostic performance.
Exploring the Pharmacokinetics of Phenoxymethylpenicillin (Penicillin-V) in Adults: A Healthy Volunteer Study
Authors: Rawson Timothy M , Wilson Richard C , Moore Luke S P , Macgowan Alasdair P , Lovering Andrew M , Bayliss Mark , Kyriakides Mathew , Gilchrist Mark , Roberts Jason A , Hope William W , Holmes Alison H
Published: December 2021

This healthy volunteer study aimed to explore phenoxymethylpenicillin (penicillin-V) pharmacokinetics (PK) to support the planning of large dosing studies in adults. Volunteers were dosed with penicillin-V at steady state. Total and unbound penicillin-V serum concentrations were determined, and a base population PK model was fitted to the data.
If Not Now, When? Nonserotype Pneumococcal Protein Vaccines
Authors: McDaniel Larry S , Swiatlo Edwin
Published: December 2021

The sudden emergence and global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have greatly accelerated the adoption of novel vaccine strategies, which otherwise would have likely languished for years. In this light, vaccines for certain other pathogens could certainly benefit from reconsideration. One such pathogen is Streptococcus pneumoniae (pneumococcus), an encapsulated bacterium that can express >100 antigenically distinct serotypes. Current pneumococcal vaccines are based exclusively on capsular polysaccharide—either purified alone or conjugated to protein. Since the introduction of conjugate vaccines, the valence of pneumococcal vaccines has steadily increased, as has the associated complexity and cost of production. There are many pneumococcal proteins invariantly expressed across all serotypes, which have been shown to induce robust immune responses in animal models. These proteins could be readily produced using recombinant DNA technology or by mRNA technology currently used in SARS-CoV-2 vaccines. A door may be opening to new opportunities in affordable and broadly protective vaccines.
Clarithromycin–Rifampin-Based Treatment for Nontuberculous Mycobacteria Infections in Immunocompromised Patients who Require Concomitant CYP-Metabolized Medications
Authors: Gonzalez-Bocco Isabel H , Aleissa Muneerah M , Zhou Eric , Manne-Goehler Jennifer , Koo Sophia , Cheng Matthew P , Marty Francisco M
Published: December 2021

Clarithromycin (CYP inhibitor) can be used instead of azithromycin for nontuberculous mycobacteria therapy in patients requiring CYP substrates to mitigate rifampin’s CYP induction. We found no differences in adverse events (10/13 vs 14/17; P = .73), drug intolerability (1/5 vs 4/11; P = 1), or 90-day mortality (0/13 vs 1/17; P = 1) in patients receiving clarithromycin vs azithromycin.
Distribution of Aspergillus Species and Prevalence of Azole Resistance in Respiratory Samples From Swiss Tertiary Care Hospitals
Authors: Ragozzino Silvio , Goldenberger Daniel , Wright Patrick R , Zimmerli Stefan , Mühlethaler Konrad , Neofytos Dionysios , Riat Arnaud , Boggian Katia , Nolte Oliver , Conen Anna , Fankhauser Hans , Schreiber Peter W , Zbinden Reinhard , Lamoth Frederic , Khanna Nina
Published: December 2021

Among 400 Aspergillus species from respiratory samples in Switzerland, Aspergillus fumigatus was the most frequent species. Non-fumigatus Aspergillus spp were more prevalent among solid organ transplant recipients and after azole exposure. Azole resistance was detected in 4 A fumigatus isolates, 3 of them with the “environmental” mutation TR34/L98H in the cyp51A gene.
Switzerland, Borneo and the Dutch Indies: Towards a New Imperial History of Europe, c.1770–1850
Authors: Schär Bernhard C
Published: December 2021

When Switzerland was created in 1848, one of its founding fathers went by the name of ‘Borneo Louis’. Before becoming a Swiss state builder, he had served as a mercenary in the Dutch East Indies. There he had founded a family with his native ‘housekeeper’, Silla. In Switzerland, he continued to benefit from Silla’s exploited labour.

Stories such as these seem unusual today, not for historical but for historiographical reasons. Borneo Louis was only one of c.70,000 mercenaries from all over Europe in Dutch imperial services. Silla was one of the countless ‘native concubines’ who were forced to support these men and thereby help the Dutch build their nineteenth-century empire in South East Asia. Other empires, too, depended on auxiliary services from Europeans hailing from regions with intra-European or short-lived empires, or none at all. Recent new imperial histories, however, have remained conceptually limited to the study of interconnections within national empires (mostly the British Empire). Pan-European dimensions of colonial histories have continued to lie outside their focus. Explaining how Switzerland became part of the Dutch imperial project, this article therefore calls for a renewed new imperial history: a history that explains how Europe emerged out of continuous connections across the boundaries of national empires.
The two clock proteins CCA1 and LHY activate VIN3 transcription during vernalization through the vernalization-responsive cis-element
Authors: Kyung Jinseul , Jeon Myeongjune , Jeong Goowon , Shin Yourae , Seo Eunjoo , Yu Jihyeon , Kim Hoyeun , Park Chung-Mo , Hwang Daehee , Lee Ilha
Published: December 2021

Vernalization, a long-term cold-mediated acquisition of flowering competence, is critically regulated by VERNALIZATION INSENSITIVE 3 (VIN3), a gene induced by vernalization in Arabidopsis. Although the function of VIN3 has been extensively studied, how VIN3 expression itself is upregulated by long-term cold is not well understood. In this study, we identified a vernalization-responsive cis-element in the VIN3 promoter, VREVIN3, composed of a G-box and an evening element (EE). Mutations in either the G-box or the EE prevented VIN3 expression from being fully induced upon vernalization, leading to defects in the vernalization response. We determined that the core clock proteins CIRCADIAN CLOCK-ASSOCIATED 1 (CCA1) and LATE-ELONGATED HYPOCOTYL (LHY) associate with the EE of VREVIN3, both in vitro and in vivo. In a cca1 lhy double mutant background harboring a functional FRIGIDA allele, long-term cold-mediated VIN3 induction and acceleration of flowering were impaired, especially under mild cold conditions such as at 12°C. During prolonged cold exposure, oscillations of CCA1/LHY transcripts were altered, while CCA1 abundance increased at dusk, coinciding with the diurnal peak of VIN3 transcripts. We propose that modulation of the clock proteins CCA1 and LHY participates in the systems involved in sensing long-term cold for the activation of VIN3 transcription.
ENB1 encodes a cellulose synthase 5 that directs synthesis of cell wall ingrowths in maize basal endosperm transfer cells
Authors: Wang Qun , Wang Mingmin , Chen Jian , Qi Weiwei , Lai Jinsheng , Ma Zeyang , Song Rentao
Published: December 2021

Development of the endosperm is strikingly different in monocots and dicots: it often manifests as a persistent tissue in the former and transient tissue in the latter. Little is known about the controlling mechanisms responsible for these different outcomes. Here we characterized a maize (Zea mays) mutant, endosperm breakdown1 (enb1), in which the typically persistent endosperm (PE) was drastically degraded during kernel development. ENB1 encodes a cellulose synthase 5 that is predominantly expressed in the basal endosperm transfer layer (BETL) of endosperm cells. Loss of ENB1 function caused a drastic reduction in formation of flange cell wall ingrowths (ingrowths) in BETL cells. Defective ingrowths impair nutrient uptake, leading to premature utilization of endosperm starch to nourish the embryo. Similarly, developing wild-type kernels cultured in vitro with a low level of sucrose manifested early endosperm breakdown. ENB1 expression is induced by sucrose via the BETL-specific Myb-Related Protein1 transcription factor. Overexpression of ENB1 enhanced development of flange ingrowths, facilitating sucrose transport into BETL cells and increasing kernel weight. The results demonstrated that ENB1 enhances sucrose supply to the endosperm and contributes to a PE in the kernel.
Investigation of the Effect of Human Milk Expression Techniques on Milk Content: A Systematic Review
Authors: Çınar Nursan , Karakaya Suzan Özge , Kaya Özge , Karataş Hülya , Duken Mehmet Emin
Published: December 2021

Background

If the mother and infant cannot meet after birth, it is recommended to express milk and give it to the infant. There was evidence indicating that there might be decrease in essential nutrient values in human milk content depending on the expression technique in literature. The goal of this systematic review was to investigate the effect of human milk expression techniques on the macronutrient milk content and establish an evidence base for future studies.

Methods

Studies investigating the effect of human milk expression techniques on milk content were reviewed without year limitations. A literature review was conducted in six electronic databases (MEDLINE, Web of Science, PubMed, ScienceDirect, CINAHL and Cochrane) until 30 May 2021, using the keywords of breast milk expression techniques, milk content and breast milk pumping.

Results

From 258 articles initially screened, we included 6 articles in the systematic review. The fat, protein and lactose content of human milk was analyzed in the studies reviewed. It was concluded that there was no significant effect on the protein (9.7–9.8 g/dl and 2.1–2.1 g/dl, respectively) and lactose (6.50–6.53% and 6.1–6.1 g/dl, respectively) content of milk. However, the fat (58.30, 48.81g/l; 2.6–2.2 g/dl) content was affected.

Conclusions

This study investigated the effect of milk expression techniques on the macronutrient content of human milk, and it was concluded that there was no significant effect on the protein and carbohydrate content of milk. However, the fat content was affected. Limitation of this study is that some factors that might affect the content of human milk were not standardized sufficiently in the included studies.
A third vaccination with a single T cell epitope protects against SARS-CoV-2 infection in the absence of neutralizing antibodies
Authors: Pardieck Iris N. , van der Gracht Esmé T.I. , Veerkamp Dominique M.B. , Behr Felix M. , van Duikeren Suzanne , Beyrend Guillaume , Rip Jasper , Nadafi Reza , van der Sluis Tetje C. , Nejad Elham Beyranvand , Mülling Nils , Brasem Dena J. , Camps Marcel G.M. , Myeni Sebenzile K. , Bredenbeek Peter J. , Kikkert Marjolein , Kim Yeonsu , Cicin-Sain Luka , Abdelaal Tamim , van Gisbergen Klaas P.J.M. , Franken Kees L.M.C. , Drijfhout Jan Wouter , Melief Cornelius J.M. , Zondag Gerben C.M. , Ossendorp Ferry , Arens Ramon
Published: December 2021

Understanding the mechanisms and impact of booster vaccinations can facilitate decisions on vaccination programmes. This study shows that three doses of the same synthetic peptide vaccine eliciting an exclusive CD8+ T cell response against one SARS-CoV-2 Spike epitope protected all mice against lethal SARS-CoV-2 infection in the K18-hACE2 transgenic mouse model in the absence of neutralizing antibodies, while only a second vaccination with this T cell vaccine was insufficient to provide protection. The third vaccine dose of the single T cell epitope peptide resulted in superior generation of effector-memory T cells in the circulation and tissue-resident memory T (TRM) cells, and these tertiary vaccine-specific CD8+ T cells were characterized by enhanced polyfunctional cytokine production. Moreover, fate mapping showed that a substantial fraction of the tertiary effector-memory CD8+ T cells developed from remigrated TRM cells. Thus, repeated booster vaccinations quantitatively and qualitatively improve the CD8+ T cell response leading to protection against otherwise lethal SARS-CoV-2 infection.

A third dose with a single T cell epitope-vaccine promotes a strong increase in tissue-resident memory CD8+ T cells and fully protects against SARS-CoV-2 infection, while single B cell epitope-eliciting vaccines are unable to provide protection.
The algal PETC-Pro171-Leu suppresses electron transfer in the cytochrome b6f complex under acidic lumenal condition
Authors: Ozawa Shin-Ichiro , Buchert Felix , Reuys Ruby , Hippler Michael , Takahashi Yuichiro
Published: December 2021

Linear photosynthetic electron flow (LEF) produces NADPH and generates a proton electrochemical potential gradient across the thylakoid membrane used to synthesize ATP, both of which are required for CO2 fixation. As cellular demand for ATP and NADPH are variable, cyclic electron flow (CEF) between PSI and cytochrome b6f complex (b6f) produces extra ATP. The b6f regulates LEF and CEF via photosynthetic control, which is a pH-dependent b6f slowdown of plastoquinol oxidation at the lumenal site. This protection mechanism is triggered at more alkaline lumen pH in the pgr1 mutant of the vascular plant Arabidopsis thaliana, carrying Pro194Leu in the b6f Rieske Iron-sulfur protein. In this work, we introduced pgr1 mutation in the green alga Chlamydomonas reinhardtii (PETC-P171L). Consistent with pgr1 phenotype, PETC-P171L displayed an impaired NPQ induction along with slower photoautotrophic growth under high light conditions. Our data provides evidence that the ΔpH component in PETC-P171L is dependent on oxygen availability. Only under low oxygen conditions the ΔpH component was sufficient to trigger a phenotype in algal PETC-P171L where the mutant b6f was more restricted to oxidize the PQ pool and showed a diminished electron flow through the b6f complex.

One sentence summary

Change of PETC to P171L via site directed mutagenesis alters the pH dependency of the photosynthetic control mechanism
Characterizing the genetic basis of trait evolution in the Mexican cavefish
Authors: Oliva Camila , Hinz Nicole K. , Robinson Wayne , Barrett Thompson Alexys M. , Booth Julianna , Crisostomo Lina M. , Zanineli Samantha , Tanner Maureen , Lloyd Evan , O’Gorman Morgan , McDole Brittnee , Paz Alexandra , Kozol Rob , Brown Elizabeth B. , Kowalko Johanna E. , Fily Yaouen , Duboue Erik R. , Keene Alex C.
Published: December 2021

Evolution in response to a change in ecology often coincides with various morphological, physiological, and behavioral traits. For most organisms little is known about the genetic and functional relationship between evolutionarily derived traits, representing a critical gap in our understanding of adaptation The Mexican tetra, Astyanax mexicanus, consists of largely independent populations of fish that inhabit at least 30 caves in Northeast Mexico, and a surface fish population, that inhabits the rivers of Mexico and Southern Texas. The recent application of molecular genetic approaches combined with behavioral phenotyping have established A. mexicanus as a model for studying the evolution of complex traits. Cave populations of A. mexicanus are interfertile with surface populations and have evolved numerous traits including eye degeneration, insomnia, albinism and enhanced mechanosensory function. The interfertility of different populations from the same species provides a unique opportunity to define the genetic relationship between evolved traits and assess the co-evolution of behavioral and morphological traits with one another. To define the relationships between morphological and behavioral traits, we developed a pipeline to test individual fish for multiple traits. This pipeline confirmed differences in locomotor activity, prey capture, and startle reflex between surface and cavefish populations. To measure the relationship between traits, individual F2 hybrid fish were characterized for locomotor behavior, prey-capture behavior, startle reflex and morphological attributes. Analysis revealed an association between body length and slower escape reflex, suggesting a trade-off between increased size and predator avoidance in cavefish. Overall, there were few associations between individual behavioral traits, or behavioral and morphological traits, suggesting independent genetic changes underlie the evolution of behavioral and morphological traits. Taken together, this approach provides a novel system to identify genes that underlie naturally occurring genetic variation in morphological and behavioral traits.
Neural signature of everyday function in older adults at-risk of cognitive impairment
Authors: De Sanctis Pierfilippo , Wagner Johanna , Molholm Sophie , Foxe John J. , Blumen Helena M. , Horsthuis Douwe J.
Published: December 2021

Assessment of everyday activities are central to the diagnosis of pre-dementia and dementia. Yet, little is known about the brain substrates and processes that contribute to everyday functional impairment, particularly during early stages of cognitive decline. We investigated everyday function using a complex gait task in normal older adults stratified by risk of cognitive impairment. We applied a novel EEG approach, which combines electroencephalographic with 3D-body tracking technology to measure brain-gait dynamics with millisecond precision while participants are in motion. Twenty-six participants (mean age = 74.9 years) with cognitive and everyday functional profiles within the normal range for their age and sex were ranked for risk of cognitive impairment. We used the Montreal Cognitive Assessment battery, a global index of cognition with a range from 0 to 30, to classify individuals as being at higher (22-26) and lower risk (27+). Individuals walking on a treadmill were exposed to visual perturbation designed to destabilize gait. Assuming that brain changes precede behavioral decline, we predicted that older adults increase step width to gain stability, yet the underlying neural signatures would be different for lower versus higher risk individuals. When pooling across risk groups, we found that step width increased and fronto-parietal activation shifted from transient, during swing phases, to sustained across the gait cycle during visually perturbed input. As predicted, step width increased in both groups but underlying neural signatures were different. Fronto-medial theta (3-7Hz) power of gait-related brain oscillations were increased in higher risk individuals during both perturbed and unperturbed inputs. On the other hand, left central gyri beta (13-28Hz) power was decreased in lower risk individuals, specifically during visually perturbed input. Finally, relating MoCA scores to spectral power pooled across fronto-parietal regions, we found associations between increased theta power and worse MoCA scores and between decreased beta power and better MoCA scores.Able-bodied older adults at-risk of cognitive impairment are characterized by unique neural signatures of mobility. Stronger reliance on frontomedial theta activation in at-risk individuals may reflect higher-order compensatory responses for deterioration of basic sensorimotor processes. Region and spectral-specific signatures of mobility may provide brain targets for early intervention against everyday functional decline.
The first Miocene fossils from coastal woodlands in the southern East African Rift
Authors: Bobe René , Aldeias Vera , Alemseged Zeresenay , Archer Will , Aumaître Georges , Bamford Marion K. , Biro Dora , Bourlès Didier L. , Braun David R. , Capelli Cristian , d’Oliveira Coelho João , Habermann Jörg M. , Head Jason J. , Keddadouche Karim , Kupczik Kornelius , Lebatard Anne-Elisabeth , Lüdecke Tina , Macôa Amélia , Martínez Felipe I. , Mathe Jacinto , Mendes Clara , Meira Paulo Luis , Pinto Maria , Püschel Thomas A. , Tátá Regala Frederico , Sier Mark , Ferreira da Silva Maria Joana , Stalmans Marc , Carvalho Susana
Published: December 2021

The Miocene is a key time in the evolution of African mammals and their ecosystems witnessing the origin of the African apes and the isolation of eastern coastal forests through an expanding biogeographic arid corridor. Until recently, however, Miocene sites from the southeastern regions of the continent were unknown. Here we report discovery of the first Miocene fossil teeth from the shoulders of the Urema Rift in Gorongosa National Park, Mozambique, at the southern East African Rift System. We provide the first 1) radiometric age determinations of the fossiliferous Mazamba Formation, 2) reconstructions of past vegetation in the region based on pedogenic carbonates and fossil wood, and 3) description of fossil teeth from the southern rift. Gorongosa is unique in the East African Rift System in combining marine invertebrates, marine vertebrates, terrestrial mammals, and fossil woods in coastal paleoenvironments. The Gorongosa fossil sites offer the first evidence of persistent woodlands and forests on the coastal margins of southeastern Africa during the Miocene, and an exceptional assemblage of fossil vertebrates including new species. Further work will allow the testing of hypotheses positing the formation of a northeast-southwest arid corridor isolating species on the eastern coastal forests from those elsewhere in Africa.

Brief

The Miocene is a key time in the evolution of African mammals and their ecosystems encompassing hominine origins and the establishment of an arid corridor that isolated eastern Africa’s coastal forests. Until now, however, Miocene sites from southeastern Africa have been unknown. We report the discovery of the first Miocene fossil sites from Gorongosa National Park, Mozambique, and show that these sites formed in coastal settings. We provide radiometric ages for the fossiliferous sediments, reconstructions of past vegetation based on stable isotopes and fossil wood, and a description of the first fossil teeth from the region. Gorongosa is the only paleontological site in the East African Rift that combines fossil woods, marine invertebrates, marine vertebrates, and terrestrial mammals. Gorongosa offers the first evidence of persistent woodlands and forests on the coastal margins of southeastern Africa during the Miocene.
Structure of EPCR in a non-canonical conformation
Authors: Erausquin Elena , Rodríguez-Fernández Adela , López-Sagaseta Jacinto
Published: December 2021

Structural motion and conformational flexibility are often linked to biological functions of proteins. Whether the endothelial protein C receptor (EPCR), like other molecules, is vulnerable to folding transitions or might adopt alternative conformations remains unknown. The current understanding points to a rigid molecular structure suitable for binding of its ligands, like the anticoagulant protein C, or the CIDRα1 domains of Plasmodium falciparum. In this study, we have identified a novel conformation of EPCR, captured by X-ray diffraction analyses, whereby Tyr154 shows a dramatically altered structural arrangement, likely incompatible with protein C binding. Biolayer interferometry analysis confirms previous results supporting a critical role for this position in protein C binding. Importantly, the conformational change has no apparent effect in the bound lipid. We conclude these findings reveal a site of conformational vulnerability in EPCR and inform a highly malleable region that could modulate EPCR functions.
Low Frequency Oscillations drive EEG’s complexity changes during wakefulness and sleep
Authors: González Joaquín , Mateos Diego , Cavelli Matias , Mondino Alejandra , Pascovich Claudia , Torterolo Pablo , Rubido Nicolás
Published: December 2021

Recently, the sleep-wake states have been analysed using novel complexity measures, complementing the classical analysis of EEGs by frequency bands. This new approach consistently shows a decrease in EEG’s complexity during slow-wave sleep, yet it is unclear how cortical oscillations shape these complexity variations. In this work, we analyse how the frequency content of brain signals affects the complexity estimates in freely moving rats. We find that the low-frequency spectrum – including the Delta, Theta, and Sigma frequency bands – drives the complexity changes during the sleep-wake states. This happens because low-frequency oscillations emerge from neuronal population patterns, as we show by recovering the complexity variations during the sleep-wake cycle from micro, meso, and macroscopic recordings. Moreover, we find that the lower frequencies reveal synchronisation patterns across the neocortex, such as a sensory-motor decoupling that happens during REM sleep. Overall, our works shows that EEG’s low frequencies are critical in shaping the sleep-wake states’ complexity across cortical scales.
Proteolytic cleavage of the extracellular domain affects signaling of parathyroid hormone receptor 1
Authors: Klenk Christoph , Hommers Leif , Lohse Martin J.
Published: December 2021

Parathyroid hormone 1 receptor (PTH1R) is a member of the class B family of G protein-coupled receptors, which are characterized by a large extracellular domain required for ligand binding. We have previously shown that the extracellular domain of PTH1R is subject to metalloproteinase cleavage in vivo that is regulated by ligand-induced receptor trafficking and leads to impaired stability of PTH1R. In this work, we localize the cleavage site in the first loop of the extracellular domain using amino-terminal protein sequencing of purified receptor and by mutagenesis studies. We further show, that a receptor mutant not susceptible to proteolytic cleavage exhibits reduced signaling to Gs and increased activation of Gq compared to wild-type PTH1R. These findings indicate that the extracellular domain modulates PTH1R signaling specificity, and that its cleavage affects receptor signaling.
Accumulation of Treg cells is detrimental in late-onset (aged) mouse model of multiple sclerosis
Authors: Wang Weikan , Thomas Rachel , Oh Jiyoung , Su Dong-Ming
Published: December 2021

Although typically associated with onset in young adults, multiple sclerosis (MS) also attacks aged people, which is termed late-onset MS. The disease can be recapitulated and studied in the aged mouse model of experimental autoimmune encephalomyelitis (EAE). The onset of induced EAE is delayed in aged mice, but the disease severity is increased relative to standard EAE in young mice. Given that CD4+FoxP3+ regulatory T (Treg) cells play an ameliorative role in MS/EAE severity and the aged immune system accumulates Treg cells, failure of these cells to prevent or ameliorate EAE disease is enigmatic. When analyzing the distribution of Treg cells in EAE mice, the aged mice exhibited a higher proportion of polyclonal(pan) Treg cells and a lower proportion of antigen-specific-Treg cells in their periphery, but lower proportions of pan- and antigen-specific-Treg cells in the central nervous system (CNS). Furthermore, in the aged CNS, Treg cells exhibited a higher plasticity and T effector (Teff) cells exhibited a greater clonal expansion, which disrupted the Treg/Teff balance. Transiently inhibiting FoxP3 expression in peripheral Treg cells partially ameliorated the disease and corrected Treg distribution in the aged mice. These results provide evidence that accumulated aged Treg cells play a detrimental role in neuronal inflammation of aged MS.

Highlights

Question

CD4+ regulatory T (Treg) cells typically play an ameliorative role in multiple sclerosis (MS) onset and severity. However, why aged immune system has accumulated peripheral Treg cells, but the elderly has more severe MS symptoms?

Findings

Aged Treg cells cannot easily distribute to the CNS of aged EAE mice, and those aged Treg cells that did enter the CNS exhibited increased plastic features. However, transient inhibition of peripherally accumulated Treg cells corrected Treg distribution and partially ameliorated the disease in the aged mice.

Conclusion and mechanistic insights

Accumulated aged Treg cells within an “inflammaging” condition do not play an ameliorative role but are potentially detrimental for inflamed CNS repair processes in aged EAE mice due to impeding the trafficking of immune cells into the inflamed CNS.
LY6S, a New Interferon-Inducible Human Member of the Ly6a-Subfamily Expressed by Spleen Cells and Associated with Inflammation and Viral Resistance
Authors: Shmerling Moriya , Chalik Michael , Smorodinsky Nechama I. , Meeker Alan , Roy Sujayita , Sagi-Assif Orit , Meshel Tsipi , Danilevsky Artem , Shomron Noam , Levinger Shmuel , Nishry Bar , Baruchi David , Shargorodsky Avital , Ziv Ravit , Sarusi-Portuguez Avital , Lahav Maoz , Ehrlich Marcelo , Braschi Bryony , Bruford Elspeth , Witz Isaac P. , Wreschner Daniel H.
Published: December 2021

Syntenic genomic loci on human chromosome 8 (hChr8) and mouse chromosome 15 (mChr15) code for LY6/Ly6 (lymphocyte antigen 6) family proteins. The 23 murine Ly6 family genes include eight genes that are flanked by the murine Ly6e and Ly6l genes and form an Ly6 subgroup referred to here as the Ly6a subfamily gene cluster. Ly6a, also known as Sca1 (Stem Cell Antigen-1) and TAP (T-cell activating protein), is a member of the Ly6a subfamily gene cluster. No LY6 genes have been annotated within the syntenic LY6E to LY6L human locus. We report here on LY6S, a solitary human LY6 gene that is syntenic with the murine Ly6a subfamily gene cluster, and with which it shares a common ancestry. LY6S codes for the interferon-inducible GPI-linked LY6S-iso1 protein that contains only 9 of the 10 consensus LY6 cysteine residues and is most highly expressed in a non-classical cell population. Its expression leads to distinct shifts in patterns of gene expression, particularly of genes coding for inflammatory and immune response proteins, and LY6S-iso1 expressing cells show increased resistance to viral infection. Our findings reveal the presence of a previously un-annotated human interferon-stimulated gene, LY6S, which has a one to eight ortholog relationship with the genes of the Ly6a subfamily gene cluster, is most highly expressed in spleen cells of a non-classical cell-lineage and whose expression induces viral resistance and is associated with an inflammatory phenotype and with the activation of genes that regulate immune responses.

One Sentence Summary

LY6S is a newly discovered human interferon-inducible gene associated with inflammation and with resistance to viral replication.
Characterizing the variation in chromosome structure ensembles in the context of the nuclear microenvironment
Authors: Das Priyojit , Shen Tongye , McCord Rachel Patton
Published: December 2021

Inside the nucleus, chromosomes are subjected to direct physical interaction between different components, active forces, and thermal noise, leading to the formation of an ensemble of three-dimensional structures. However, it is still not well understood to what extent and how the structural ensemble varies from one chromosome region or cell-type to another. We designed a statistical analysis technique and applied it to single-cell chromosome imaging data to reveal the heterogeneity of individual chromosome structures. By analyzing the resulting structural landscape, we find that the largest dynamic variation is the overall radius of gyration of the chromatin region, followed by domain reorganization within the region. By comparing different human cell-lines and experimental perturbation data using this statistical analysis technique and a network-based similarity quantification approach, we identify both cell-type and condition-specific features of the structural landscapes. We identify a relationship between epigenetic state and the properties of chromosome structure fluctuation and validate this relationship through polymer simulations. Overall, our study suggests that the types of variation in a chromosome structure ensemble are cell-type as well as region-specific and can be attributed to constraints placed on the structure by factors such as variation in epigenetic state.