bluuebunny/crossref_metadata_2025 huggingface dataset:
PopHumanVar: an interactive application for the functional characterization and prioritization of adaptive genomic variants in humans
Authors: Colomer-Vilaplana Aina , Murga-Moreno Jesús , Canalda-Baltrons Aleix , Inserte Clara , Soto Daniel , Coronado-Zamora Marta , Barbadilla Antonio , Casillas Sònia
Published: September 2021

Adaptive challenges that humans faced as they expanded across the globe left specific molecular footprints that can be decoded in our today's genomes. Different sets of metrics are used to identify genomic regions that have undergone selection. However, there are fewer methods capable of pinpointing the allele ultimately responsible for this selection. Here, we present PopHumanVar, an interactive online application that is designed to facilitate the exploration and thorough analysis of candidate genomic regions by integrating both functional and population genomics data currently available. PopHumanVar generates useful summary reports of prioritized variants that are putatively causal of recent selective sweeps. It compiles data and graphically represents different layers of information, including natural selection statistics, as well as functional annotations and genealogical estimations of variant age, for biallelic single nucleotide variants (SNVs) of the 1000 Genomes Project phase 3. Specifically, PopHumanVar amasses SNV-based information from GEVA, SnpEFF, GWAS Catalog, ClinVar, RegulomeDB and DisGeNET databases, as well as accurate estimations of iHS, nSL and iSAFE statistics. Notably, PopHumanVar can successfully identify known causal variants of frequently reported candidate selection regions, including EDAR in East-Asians, ACKR1 (DARC) in Africans and LCT/MCM6 in Europeans. PopHumanVar is open and freely available at https://pophumanvar.uab.cat.
scMRMA: single cell multiresolution marker-based annotation
Authors: Li Jia , Sheng Quanhu , Shyr Yu , Liu Qi
Published: September 2021

Single-cell RNA sequencing has become a powerful tool for identifying and characterizing cellular heterogeneity. One essential step to understanding cellular heterogeneity is determining cell identities. The widely used strategy predicts identities by projecting cells or cell clusters unidirectionally against a reference to find the best match. Here, we develop a bidirectional method, scMRMA, where a hierarchical reference guides iterative clustering and deep annotation with enhanced resolutions. Taking full advantage of the reference, scMRMA greatly improves the annotation accuracy. scMRMA achieved better performance than existing methods in four benchmark datasets and successfully revealed the expansion of CD8 T cell populations in squamous cell carcinoma after anti-PD-1 treatment.
The human pseudouridine synthase PUS7 recognizes RNA with an extended multi-domain binding surface
Authors: Guegueniat Julia , Halabelian Levon , Zeng Hong , Dong Aiping , Li Yanjun , Wu Hong , Arrowsmith Cheryl H , Kothe Ute
Published: September 2021

The human pseudouridine synthase PUS7 is a versatile RNA modification enzyme targeting many RNAs thereby playing a critical role in development and brain function. Whereas all target RNAs of PUS7 share a consensus sequence, additional recognition elements are likely required, and the structural basis for RNA binding by PUS7 is unknown. Here, we characterize the structure–function relationship of human PUS7 reporting its X-ray crystal structure at 2.26 Å resolution. Compared to its bacterial homolog, human PUS7 possesses two additional subdomains, and structural modeling studies suggest that these subdomains contribute to tRNA recognition through increased interactions along the tRNA substrate. Consistent with our modeling, we find that all structural elements of tRNA are required for productive interaction with PUS7 as the consensus sequence of target RNA alone is not sufficient for pseudouridylation by human PUS7. Moreover, PUS7 binds several, non-modifiable RNAs with medium affinity which likely enables PUS7 to screen for productive RNA substrates. Following tRNA modification, the product tRNA has a significantly lower affinity for PUS7 facilitating its dissociation. Taken together our studies suggest a combination of structure-specific and sequence-specific RNA recognition by PUS7 and provide mechanistic insight into its function.
Impact of obesity in kidney transplantation: a prospective cohort study from French registries between 2008 and 2014
Authors: Grèze Clarisse , Pereira Bruno , Boirie Yves , Guy Laurent , Millet Clémentine , Clerfond Guillaume , Garrouste Cyril , Heng Anne-Elisabeth
Published: September 2021

Background

The access of obese patients to kidney transplantation is limited despite several studies showing that obese transplant recipients had a better survival rate than those undergoing dialysis. The aim of this study was to compare patient and graft survival rates and post-renal transplant complications in obese patients and non-obese patients and to assess the effect of pre-transplant weight loss in obese patients on transplant outcomes.

Methods

We carried out a prospective cohort study using two French registries, the Renal Epidemiology and Information Network and CRISTAL, on 7270 kidney transplant patients between 2008 and 2014 in France. We compared obese patients with non-obese patients and obese patients who lost more than 10% of weight before the transplant (obese WL and obese nWL).

Results

The mean BMI in our obese patients was 32 kg/m2. Graft survival was lower in obese patients than in non-obese patients {hazard ratio (HR) = 1.40, [95% confidence interval (95% CI) 1.09; 1.78], P = 0.007}, whereas patient survival was similar [HR = 0.94, (95% CI 0.73; 1.23), P = 0.66]. Graft survival was significantly lower in obese WL than in obese nWL [HR = 2.17, (1.02; 4.63), P = 0.045], whereas patient survival was similar in the two groups [HR = 0.79, (0.35; 1.77), P = 0.56].

Conclusion

Grade 1 obesity does not seem to be a risk factor for excess mortality after kidney transplantation and should not be an obstacle to having access to a graft. Weight loss before a kidney transplant in these patients should not be essential for registration on waiting list.
Seizures in patients with kidney diseases: a neglected problem?
Authors: Gungor Ozkan , Aydin Zeki , Inci Ayca , Oguz Ebru Gok , Arici Mustafa
Published: September 2021

Nephrologists may encounter many systemic problems in their patients, including involvement of the neurological system and the development of seizures. Seizures are defined as abnormal neurological functions that cause overstimulation of neurons in the cerebral cortex or limbic system. Seizures may be focal or generalized depending on their origin and may have tonic, clonic, tonic–clonic or myoclonic character depending on the level of involvement of the motor movements. Patients with kidney disease may develop seizures due to etiologies seen in the general population (such as intracranial bleeding, cerebrovascular events, tumors, infections and intoxications) or due to kidney-related etiologies (such as uremic encephalopathy, dialysis disequilibrium syndrome and hyponatremia). Management of seizures in kidney patients is challenging for proper determination of the type and dosage of antiepileptic drugs due to varying renal clearances. This review covers the major causes of new-onset seizures in patients with acute kidney injury, electrolyte imbalances, chronic kidney disease, dialysis, renal transplantation or hypertension, and the available management approaches.
Dust dissipation timescales in the intermediate and outer regions of protoplanetary disks
Authors: Maeshima Hiroshi , Nakagawa Takao , Kojima Takuya , Takita Satoshi , Kwon Jungmi
Published: September 2021

Dust and gas in protoplanetary disks dissipate as central stars evolve. In order to estimate the dust dissipation timescales in the protoplanetary disks, we stacked the WISE 12 and 22, and the AKARI 90 μm survey images of known T Tauri stars and derived the average fluxes, well below the survey flux limit in the 90 μm band. We classified 4783 T Tauri stars into three age groups, which are young (<2 Myr), mid-age (2–6 Myr), and old (>6 Myr) groups, and stacked the WISE 12 and 22 and the AKARI 90 μm images in each group. The photometry of the stacked image shows the flux decay timescales of 1.4 ± 0.2, 1.38 ± 0.05, and $1.4^{+0.6}_{-0.5}\:$Myr in the 12, 22, and 90 μm bands, respectively. In optically thin disks with one-solar luminosity central stars, the 12 and 22 μm fluxes are attributed to the emission from the intermediate (∼1 au) region and the 90 μm flux corresponds to that from the outer (∼10 au) region in the disk. We hence conclude that the dust dissipation timescale is τmed,dust ∼ 1.4 Myr in the intermediate disks and is $\tau _{\rm outer,dust}= 1.4^{+0.6}_{-0.5}\:$Myr in the outer disks. The dust-dissipation time difference between the outer and intermediate disks is $\Delta \tau _{\rm dust} = \tau _{\rm outer,dust} -\tau _{\rm med,dust}=0.0^{+0.6}_{-0.5}\:$Myr, indicating that the dust in the intermediate and outer disks dissipates on almost the same timescale.
The rôles of plankton and neuston microbial organic matter in climate regulation
Authors: Jenkinson Ian R , Berdalet Elisa , Chin Wei-Chun , Denis Michel , Ding Haibing , Duan Jizhou , Elias Florence , Emri Igor , Karn Santosh K , Li Zhuo , Malej Alenka , Mari Xavier , Seuront Laurent , Sun Jun , Wyatt Tim , Zhang Wuchang , Wurl Oliver
Published: September 2021

Plankton and neuston microbes produce organic matter (OM), which accumulates in the sea surface microlayer (SML). Fluxes of heat and momentum exchange across the sea-air interface, as do fluxes of matter, including greenhouse gases, aerosols, microbes (algae, bacteria sensu lato and viruses) and other substances. At least at calm to moderate windspeeds, microbial OM (MOM) in the SML reduces these fluxes. Another MOM fraction, foam, covers a part of the ocean surface. Ocean foam increases mean ocean albedo because it reflects solar radiation, thus cooling the ocean and the Earth. The rheological properties of MOM and the reduction of sea-air fluxes depend on microbial abundance and taxonomic composition, as do the formation and persistence of foam. Genomic regulation of MOM secretion may thus be helping to regulate air-sea fluxes and climate. Unpredictable changes in abundance and taxonomic composition of these microbial communities may be adding uncertainty to global and more local climate. Some of this uncertainty could be mitigated by studying the ecology and genomics of the surface microbial community together with chemical and rheological properties of their secreted MOM and its effects on sea-air fluxes and foam coverage, to incorporate into climate models.
SlKIX8 and SlKIX9 are negative regulators of leaf and fruit growth in tomato
Authors: Swinnen Gwen , Mauxion Jean-Philippe , Baekelandt Alexandra , De Clercq Rebecca , Van Doorsselaere Jan , Inzé Dirk , Gonzalez Nathalie , Goossens Alain , Pauwels Laurens
Published: September 2021

Plant organ size and shape are major agronomic traits that depend on cell division and expansion, which are both regulated by complex gene networks. In several eudicot species belonging to the rosid clade, organ growth is controlled by a repressor complex consisting of PEAPOD (PPD) and KINASE-INDUCIBLE DOMAIN INTERACTING (KIX) proteins. The role of these proteins in asterids, which together with the rosids constitute most of the core eudicot species, is unknown. We used Clustered Regularly Interspaced Short Palindromic Repeats–CRISPR-associated protein 9 genome editing to target SlKIX8 and SlKIX9 in the asterid model species tomato (Solanum lycopersicum) and analyzed loss-of-function phenotypes. Loss-of-function of SlKIX8 and SlKIX9 led to the production of enlarged, dome-shaped leaves and these leaves exhibited increased expression of putative Solanum lycopersicum PPD (SlPPD target genes. Unexpectedly, kix8 kix9 mutants carried enlarged fruits with increased pericarp thickness due to cell expansion. At the molecular level, protein interaction assays indicated that SlKIX8 and SlKIX9 act as adaptors between the SlPPD and SlTOPLESS co-repressor proteins. Our results show that KIX8 and KIX9 are regulators of organ growth in asterids and can be used in strategies to improve important traits in produce such as thickness of the fruit flesh.
Continuous Pecto-Intercostal Fascial Block Provides Effective Analgesia in Patients Undergoing Open Cardiac Surgery: A Randomized Controlled Trial
Authors: Zhang Yang , Min Jia , Chen Shibiao
Published: September 2021

Background

The optimal analgesia regimen after open cardiac surgery has been unclear. The aim of this study was to investigate the beneficial effects of continuous pecto-intercostal fascial blocks (PIFB) initiated before surgery on outcomes after open cardiac surgery.

Methods

A group of 116 patients were randomly allocated to receive either bilateral continuous PIFB (PIF group) or the same block with saline (SAL group). The primary endpoint was postoperative pain at 4, 8, 16, 24, 48, and 72 hours after extubation at rest and during exercise. The secondary outcome measures included analgesia requirements (sufentanil and flurbiprofen consumption), time to extubation, length of stay in the intensive care unit, incidence of postoperative nausea and vomiting, time until return of bowel function, time to mobilization, time to urinary catheter removal, and the length of hospital stay.

Results

The length of stay in the intensive care unit (29 ± 7 hours vs 13 ± 4 hours, P < 0.01) and length of hospital stay (8.9 ± 0.9 days vs 6.5 ± 1.1 days, P < 0.01) were significantly longer in the SAL group than in the PIF group. Resting pain scores (2 hours after extubation: 1.1 vs 3.3, P < 0.01; 4 hours after extubation: 1.0 vs 3.5, P < 0.01; 8 hours after extubation: 1.2 vs 3.7, P < 0.01; 16 hours after extubation: 1.3 vs 3.7, P < 0.01; 24 hours after extubation: 1.4 vs 2.8, P < 0.01; 48 hours after extubation: 0.9 vs 2.2, P < 0.01; 72 hours after extubation: 0.8 vs 2.1, P < 0.01) and dynamic pain scores (2 hours after extubation: 1.4 vs 3.7, P < 0.01; 4 hours after extubation: 1.3 vs 3.8, P < 0.01; 8 hours after extubation: 1.4 vs 3.5, P < 0.01; 16 hours after extubation: 1.2 vs 3.4, P < 0.01; 24 hours after extubation: 1.1 vs 3.1, P < 0.01; 48 hours after extubation: 1.0 vs 2.9, P < 0.01; 72 hours after extubation: 0.9 vs 2.8, P < 0.01) were significantly lower in the PIF group than in the SAL group at all time points. The PIF group required significantly less intraoperative sufentanil consumption (123 ± 32 μg vs 63 ± 16 μg, P < 0.01), postoperative sufentanil consumption (102 ± 22 μg vs 52 ± 17 μg, P < 0.01), and postoperative flurbiprofen consumption (350 ± 100 mg vs 100 ± 100 mg, P < 0.01) than the SAL groups. Time to extubation (8.9 ± 2.4 hours vs 3.2 ± 1.3 hours, P < 0.01), time to first flatus (43 ± 6 hours vs 30 ± 7 hours, P < 0.01), time until mobilization (35 ± 5 hours vs 24 ± 7 hours, P < 0.01), and time until urinary catheter removal (47 ± 9 hours vs 31 ± 4 hours, P < 0.01) were significantly earlier in the PIF group than in the SAL group. The incidence of postoperative nausea and vomiting was significantly lower in the PIF group (9.1% vs 27.3%, P < 0.01).

Conclusion

Bilateral continuous PIFB reduced the length of hospital stay and provided effective postoperative pain relief for 3 days.
The Trump Election and Attitudes toward the United States in Latin America
Authors: Carreras Miguel , Visconti Giancarlo , Acácio Igor
Published: September 2021

Did the election of Donald Trump have an immediate effect on trust in the US government in Latin America? While on the campaign trail, the Republican candidate used strong and derogatory language to describe Latin American countries and people and made policy proposals that could deteriorate US-Latin American relations. However, the effect of the Trump election on attitudes toward the United States might be null or minimal if Latin American citizens have strong priors and/or if they do not pay attention to political information. Therefore, it is not clear whether the 2016 election led to a rapid decline in trust in the US government in Latin America. Leveraging the timing of the field implementation of the 2016 wave of the AmericasBarometer in five Latin American countries, we estimate the effect of the 2016 presidential election on respondents’ attitudes using a regression discontinuity design in time. We find that the election of Trump substantively decreased respondents’ trust in the US government.
Effects of prolonged methylphenidate treatment on amygdala reactivity and connectivity: a randomized controlled trial in stimulant treatment-naive, male participants with ADHD
Authors: Kaiser Antonia , Bottelier Marco A , de Ruiter Michiel B , Solleveld Michelle M , Tamminga Hyke G H , Bouziane Cheima , Geurts Hilde M , Lindauer Ramon J L , Kooij J J Sandra , Lucassen Paul J , Schrantee Anouk , Reneman Liesbeth
Published: September 2021

Background

Problems with emotional processing are widely reported in individuals with attention-deficit/hyperactivity disorder (ADHD). Although methylphenidate (MPH) effectively alleviates inattention and hyperactivity symptoms in ADHD, its effects on emotional processing and internalizing symptoms have remained elusive. While we previously found that acute MPH administration modulated neural mechanisms underlying emotional processing in an age-dependent manner, the effects of prolonged administration remained unknown.

Objectives

Therefore, we investigated: (i) whether prolonged MPH treatment influences neural substrates (amygdala reactivity and connectivity) of emotional processing, and (ii) whether these effects are modulated by age.

Methods

The “effects of Psychotropic drugs On Developing brain-MPH” (“ePOD-MPH”) randomized controlled trial was a 16-week double-blind, placebo-controlled, multi-center trial with MPH in 50 boys (10–12 years of age) and 49 men (23–40 years of age), all stimulant treatment-naive and diagnosed with ADHD. Participants performed an emotional face-matching task during functional magnetic resonance imaging. We assessed their symptoms of ADHD and internalizing symptoms at baseline, during the trial (8 weeks), and 1 week after the trial end (17 weeks).

Results and Conclusions

We did not find effects of prolonged MPH treatment on emotional processing, as measured by amygdala reactivity and connectivity and internalizing symptoms in this trial with stimulant treatment-naive participants. This differs from our findings on emotional processing following acute MPH administration and the effects of prolonged MPH treatment on the dopamine system, which were both modulated by age. Interestingly, prolonged MPH treatment did improve ADHD symptoms, although depressive and anxiety symptoms showed a medication-independent decrease. Furthermore, our data indicate that baseline internalizing symptoms may be used to predict MPH treatment effects on ADHD symptoms, particularly in (male) adults with ADHD.
Measuring Operating Leverage
Authors: Chen Huafeng (Jason) , Chen Jason V , Li Feng , Li Pengfei
Published: September 2021

We examine a simple measure of operating leverage: the ratio of fixed costs (measured by depreciation and amortization plus selling, general, and administrative expenses) to the market (or book) value of assets. We find that this measure of operating leverage positively predicts returns. This operating leverage measure is not explained by common factors and performs better than the traditional measures of operating leverage. Furthermore, an exploratory two-factor model with the operating leverage factor works at least as well as, but does not subsume, the Fama and French five-factor model. (JEL G11, G12, G30)
Association between autoantibodies in systemic sclerosis and cancer in a national registry
Authors: Hoa Sabrina , Lazizi Selma , Baron Murray , Wang Mianbo , Fritzler Marvin J , Hudson Marie ,   for the Canadian Scleroderma Research Group
Published: September 2021

Objective

A close temporal relationship between SSc onset and cancer has been reported in anti-RNA polymerase III-positive patients. We investigated the association between cancer and other SSc autoantibodies in a national SSc registry.

Methods

SSc patients enrolled in the Canadian Scleroderma Research Group registry from 2004 to 2019 were characterized according to autoantibodies to centromere, topoisomerase I/Scl70, RNA polymerase III, fibrillarin, Th/To (hPOP1), PM/Scl, Ku, NOR90, Ro52/TRIM21 and U1RNP. Logistic regression was used to examine the association between a close cancer-SSc interval and autoantibody status, adjusted for age, sex, race and smoking history.

Results

Of 1698 SSc patients, 1481 (87%) had available autoantibody data. Cancer was diagnosed within 2, 3 and 5 years of the first non-Raynaud manifestation in 1.3%, 2.1% and 3.5% of patients. The most frequent cancers diagnosed within 2 years were breast (33%), gynaecological (19%) and haematological (14%) cancers. The risk of cancer within 2 years was increased among anti-topoisomerase I [odds ratio (OR) 3.43, 95% CI: 1.04, 10.05] and anti-U1-RNP-positive patients (OR 5.54, 95% CI: 1.16, 20.40), but not with anti-RNA polymerase III. None of the anti-fibrillarin, Th/To, PM/Scl, Ku and NOR90-positive patients had cancer within 2 years. Patients with anti-centromere or none of the tested autoantibodies had numerically lower risks of developing cancer within two years.

Conclusion

Synchronous cancer was rare in this large cohort of predominantly female and White SSc patients. The risk of cancer within 2 years was increased among anti-topoisomerase I and anti-U1-RNP-positive patients. Screening strategies guided by autoantibodies require further careful consideration.
Lobbying to the rhythm of Wall Street? Explaining the political advocacy of non-financial corporations over financial regulatory policy
Authors: Young Kevin L , Pagliari Stefano
Published: September 2021

Non-financial corporations (NFCs) have acted as vocal and important allies with the financial industry when it comes to advocacy over regulatory policy. Why? We explore this question in the context of the lobbying activity surrounding the financial policy reforms in the USA following the global financial crisis. We propose a range of explanations for why some NFCs might become ‘financial activists’ in support of the financial industry, while others remain passive. We find a wide range of indicators of firm-level financialization to be unreliable predictors of NFC financial activism, in addition to indicators of potential external control by financial firms through their ownership structure or the presence of financial subsidiaries. Our finding instead show how NFC financial activism is related to how a given firm is embedded in broader structures of corporate networks, relational political action, and ideology.
Analyzing Disparity and Rates of Morphological Evolution with Model-Based Phylogenetic Comparative Methods
Authors: Hansen Thomas F , Bolstad Geir H , Tsuboi Masahito
Published: September 2021

Understanding variation in rates of evolution and morphological disparity is a goal of macroevolutionary research. In a phylogenetic comparative methods framework, we present three explicit models for linking the rate of evolution of a trait to the state of another evolving trait. This allows testing hypotheses about causal influences on rates of phenotypic evolution with phylogenetic comparative data. We develop a statistical framework for fitting the models with generalized least-squares regression and use this to discuss issues and limitations in the study of rates of evolution more generally. We show that the power to detect effects on rates of evolution is low in that even strong causal effects are unlikely to explain more than a few percent of observed variance in disparity. We illustrate the models and issues by testing if rates of beak-shape evolution in birds are influenced by brain size, as may be predicted from a Baldwin effect in which presumptively more behaviorally flexible large-brained species generate more novel selection on themselves leading to higher rates of evolution. From an analysis of morphometric data for 645 species, we find evidence that both macro- and microevolution of the beak are faster in birds with larger brains, but with the caveat that there are no consistent effects of relative brain size.[Baldwin effect; beak shape; behavioral drive; bird; brain size; disparity; phylogenetic comparative method; rate of evolution.]
Time Course of Odor Categorization Processing
Authors: Bae Jisub , Kim Kwangsu , Moon Sun Ae , Choe Han Kyoung , Jin Youngsun , Kang Won-Seok , Moon Cheil
Published: September 2021

The brain’s mechanisms for categorizing different odors have long been a research focus. Previous studies suggest that odor categorization may involve multiple neurological processes within the brain with temporal and spatial neuronal activation. However, there is limited evidence regarding temporally mediated mechanisms in humans, especially millisecond odor processing. Such mechanisms may be important because different brain areas may play different roles at a particular activation time during sensory processing. Here, we focused on how the brain categorizes odors at specific time intervals. Using multivariate electroencephalography (EEG) analysis, we found that similarly perceived odors induced similar EEG signals during 50–100, 150–200, and 350–400 ms at the theta frequency. We also found significant activation at 100–150 and 350–400 ms at the gamma frequency. At these two frequencies, significant activation was observed in some olfactory-associated areas, including the orbitofrontal cortex. Our findings provide essential evidence that specific periods may be related to odor quality processing during central olfactory processing.
Epidemiological dynamics of SARS-CoV-2 VOC Gamma in Rio de Janeiro, Brazil
Authors: Moreira Filipe Romero Rebello , D’arc Mirela , Mariani Diana , Herlinger Alice Laschuk , Schiffler Francine Bittencourt , Rossi Átila Duque , Leitão Isabela de Carvalho , Miranda Thamiris dos Santos , Cosentino Matheus Augusto Calvano , Tôrres Marcelo Calado de Paula , da Costa Raíssa Mirella dos Santos Cunha , Gonçalves Cássia Cristina Alves , Faffe Débora Souza , Galliez Rafael Mello , Junior Orlando da Costa Ferreira , Aguiar Renato Santana , Dos Santos André Felipe Andrade , Voloch Carolina Moreira , Castiñeiras Terezinha Marta Pereira Pinto , Tanuri Amilcar
Published: September 2021

The emergence and widespread circulation of severe acute respiratory syndrome coronavirus 2 variants of concern (VOCs) or interest impose an enhanced threat to global public health. In Brazil, one of the countries most severely impacted throughout the pandemic, a complex dynamics involving variants co-circulation and turnover events has been recorded with the emergence and spread of VOC Gamma in Manaus in late 2020. In this context, we present a genomic epidemiology investigation based on samples collected between December 2020 and May 2021 in the second major Brazilian metropolis, Rio de Janeiro. By sequencing 244 novel genomes through all epidemiological weeks in this period, we were able to document the introduction and rapid dissemination of VOC Gamma in the city, driving the rise of the third local epidemic wave. Molecular clock analysis indicates that this variant has circulated locally since the first weeks of 2021 and only 7 weeks were necessary for it to achieve a frequency above 70 per cent, consistent with rates of growth observed in Manaus and other states. Moreover, a Bayesian phylogeographic reconstruction indicates that VOC Gamma spread throughout Brazil between December 2020 and January 2021 and that it was introduced in Rio de Janeiro through at least 13 events coming from nearly all regions of the country. Comparative analysis of reverse transcription-quantitative polymerase chain reaction (RT-qPCR) cycle threshold (Ct) values provides further evidence that VOC Gamma induces higher viral loads (N1 target; mean reduction of Ct: 2.7, 95 per cent confidence interval = ± 0.7). This analysis corroborates the previously proposed mechanistic basis for this variant-enhanced transmissibility and distinguished epidemiological behavior. Our results document the evolution of VOC Gamma and provide independent assessment of scenarios previously studied in Manaus, therefore contributing to the better understanding of the epidemiological dynamics currently being surveyed in other Brazilian regions.
Retirement Adjustment in Germany From 1996 to 2014
Authors: Henning Georg , Johansson Boo , Lindwall Magnus , Huxhold Oliver
Published: September 2021

The context of retirement has changed over the last decades, but there is little knowledge on whether the quality of retirement adjustment has changed as well. Changes in retirement regulations and historical differences in resources may affect the quality of adjustment and increase inequalities between different socioeconomic groups. In the present study, we investigated historical differences in retirement adjustment by comparing cross-sectional samples of retirees from 1996, 2002, 2008, and 2014, based on the population-based German Ageing Survey. Adjustment was measured with three different indicators (perceived change in life after retirement, retirement satisfaction, adjustment difficulties). Retirement satisfaction was higher in later samples, but for the other two outcomes, there was no evidence for systematic increases or decreases in levels of retirement adjustment with historical time over the studied period. White-collar workers reported better adjustment than blue-collar workers did, and for two of three outcomes, this effect was stable over time. The white-collar workers’ advantage concerning retirement satisfaction, however, increased. We conclude that in Germany, at least for those who retire within the usual time window, adjustment quality has not changed systematically over the examined 18-year period. We only found mixed evidence for a growing social inequality in the retirement adjustment. However, as individual agency in choosing one’s retirement timing and pathway is increasingly restricted, social inequalities in well-being before retirement may increase.
Phylogenetic analyses of a new freshwater amphipod reveal polyphyly within the Holarctic family Crangonyctidae, with revision of the genus Synurella
Authors: Cannizzaro Andrew G , Daniels James D , Berg David J
Published: September 2021

A new genus and species of crangonyctid amphipod, Sicifera cahawba gen. & sp. nov., is described from Dallas County, AL, USA, based on both morphological and molecular comparison with similar crangonyctids. These data, with the application of four species delimitation models, identify the taxon as distinct when compared with related species. Nearctic members of the crangonyctid genus Synurella form a separate, well-supported monophyletic lineage when compared with Palaearctic members, which differ considerably in both molecular and morphological markers. Nearctic members, with the exception of the enigmatic Synurella (Eosynurella) johanseni, are placed in the newly erected Sicifera. The separation of these two genera implies that Palaearctic and Nearctic crangonyctid lineages might not be as closely related as once thought, and their evolutionary and biogeographical history requires further review. In addition, a key to Nearctic members of the genera Eosynurella/Sicifera is presented to aid in future identification.
Pressure Injury Prevention for Complex Cardiovascular Patients in the Operating Room and Intensive Care Unit
Authors: Pittman Joyce , Horvath Dawn , Beeson Terrie , Bailey Karrie , Mills Annie , Kaiser Laura , Hall Deborah K. , Sweeney Jennifer
Published: September 2021

PURPOSE:

The purpose of our project was to examine the effect of an alternating pressure (AP) overlay on hospital-acquired pressure injury (HAPI) in high-risk cardiovascular surgical patients.

PARTICIPANTS AND SETTING:

This quality improvement (QI) initiative was conducted in a core group of 8 cardiovascular operating room (OR) suites and 1 cardiovascular surgical critical intensive care unit (ICU) in a large Indiana-based academic hospital. The sample comprised adult patients who underwent complex cardiovascular surgical procedures and those in the cardiovascular surgical ICU with extracorporeal membrane oxygenation (ECMO), ventricular assistive device (VAD), and undergoing heart and/or lung transplant, or open chest procedures.

APPROACH:

The AP overlay was placed on OR cardiovascular foam surfaces and on selected ICU support surfaces for patients who met inclusion criteria. We used a pre/postcomparative QI design to assess outcomes including OR-related HAPI rates, ICU aggregate unit HAPI data, related costs, and staff satisfaction during the 3-month project period.

OUTCOMES:

Operating room-related HAPIs were reduced from 8/71 (11%) preintervention to 0/147 (0%) postintervention (P = .008), resulting in a cost avoidance of $323,048 and positive staff satisfaction (mean = 3.85; 1- to 4-point Likert scale). No adverse outcomes occurred. Although not significant, ICU HAPI rates decreased from 10 to 7 pre/postintervention (P = .29), demonstrating a 14% HAPI reduction with a cost avoidance of $121,143. The ICU incidence density decreased from 3.57 to 3.24; however, there was no decrease in ICU monthly unit prevalence. Critical care staff satisfaction was positive (mean = 2.95; 1- to 4-point Likert scale) with most staff members preferring the AP overlay to a fluid immersion surface. A cost savings of 48% (AP overlay vs fluid immersion rental) was identified in the ICU.

IMPLICATIONS FOR PRACTICE:

We achieved fewer HAPIs and reduced costs and observed positive staff satisfaction, along with no adverse events with the use of the AP overlay. Further research is needed to determine the safety and efficacy of this device for this pressure injury prevention option for immobile patients in both the OR and the ICU.
First experiences of whole-head OP-MEG recordings from a patient with Epilepsy
Authors: Mellor Stephanie , Vivekananda Umesh , O’Neill George C. , Tierney Tim M. , Doig David , Seymour Robert A. , Alexander Nicholas , Walker Matthew C. , Barnes Gareth R.
Published: September 2021

Optically Pumped Magnetometer based Magnetoencephalography (OP-MEG) has significant potential for clinical use in pre-surgical planning in epilepsy. Unlike current clinical MEG, the sensors do not require cryogenic cooling and so can be placed directly on the patient’s head. This allows the patient to move during the recording and means that the sensor positions can be chosen to suit the patient’s head shape and suspected epileptogenic focus. However, OP-MEG is a new technology, and more work is needed to demonstrate this potential. We present OP-MEG recordings from a patient (male in their 30s) with a radiologically identifiable focal cortical dysplasia (FCD) in the right superior frontal sulcus approximately 1.9 cm3 in volume. Previous scalp EEG studies and prolonged video-EEG telemetry did not identify any interictal epileptiform abnormalities. We recorded 30 minutes of OP-MEG with 62-channel, whole-head sensor coverage. During the experiment, the patient’s head was unconstrained. We localised interictal epileptiform discharges (IEDs) from this recording with a beamformer and by fitting a dipole to the averaged IED data. Both the beamformer peak and dipole fit locations were within 2.3 cm of the MRI lesion boundary. This single subject, proof-of-concept recording provides further evidence that OP-MEG can be a useful and minimally invasive tool in the clinical evaluation of epilepsy.
Correlation of mitochondrial TOM core complex stop-and-go and open-closed channel dynamics
Authors: Wang Shuo , Findeisen Lukas , Leptihn Sebastian , Wallace Mark I. , Hörning Marcel , Nussberger Stephan
Published: September 2021

The role of lateral diffusion of proteins in the membrane in the context of function has not been examined extensively. Here, we explore the relationship between protein lateral diffusion and channel activity of the general protein import pore of mitochondria (TOM-CC). Optical ion flux sensing through single TOM-CC molecules shows that TOM-CC can occupy three ion permeability states. Whereas freely diffusing TOM-CC molecules are preferentially found in a high permeability state, physical tethering to an agarose support causes the channels to transition to intermediate and low permeability states. This data shows that combinatorial opening and closing of the two pores of TOM-CC correlates with lateral protein diffusion in the membrane plane, and that the complex has mechanosensitive-like properties. This is the first demonstration of β-barrel protein mechanosensitivity, and has direct conceptual consequences for the understanding of the process of mitochondrial protein import. Our approach provides a novel tool to simultaneously study the interplay of membrane protein diffusion and channel dynamics.
Single-nucleus transcriptomic atlas of spinal cord neuron in human
Authors: Zhang Donghang , Wei Yiyong , Liu Jin , Chen Hongjun , Li Jin , Zhu Tao , Zhou Cheng
Published: September 2021

Despite the recognized importance of spinal cord in sensory processing, motor behaviors and/or neural diseases, the underlying neuronal clusters remain elusive. Recently, several studies attempted to define the neuronal types and functional heterogeneity in spinal cord using single cell and/or single-nucleus RNA-sequencing in varied animal models. However, the molecular evidence of neuronal heterogeneity in human spinal cord has not been established yet. Here we sought to classify spinal cord neurons from human donors by high-throughput single-nucleus RNA-sequencing. The functional heterogeneity of identified cell types and signaling pathways that connecting neuronal subtypes were explored. Moreover, we also compared human results with previous single-cell transcriptomic profiles of mouse spinal cord. As a result, we generated the first comprehensive atlas of human spinal cord neurons and defined 18 neuronal clusters. In addition to identification of the new and functionally-distinct neuronal subtypes, our results also provide novel marker genes for previously known neuronal types. The comparation with mouse transcriptomic profiles revealed an overall similarity in the cellular composition of spinal cord between the two species. In summary, these results illustrate the complexity and diversity of neuronal types in human spinal cord and will provide an important resource for future researches to explore the molecular mechanism underlying several spinal cord physiology and diseases.
Muscle group specific transcriptomic and DNA methylation differences related to developmental patterning in FSHD
Authors: Williams Katherine , Kong Xiangduo , Nguyen Nam Viet , McGill Cassandra , Tawil Rabi , Yokomori Kyoko , Mortazavi Ali
Published: September 2021

Muscle groups throughout the body are specialized in function and are specified during development by position specific gene regulatory networks. In developed tissue, myopathies affect muscle groups differently. Facioscapulohumeral muscular dystrophy, FSHD, affects upper body and tibialis anterior (TA) muscles earlier and more severely than others such as quadriceps. To investigate an epigenetic basis for susceptibility of certain muscle groups to disease, we perform DNA methylation and RNA sequencing on primary patient derived myoblasts from TA and quadricep for both control and FSHD2 as well as RNA-seq for myoblasts from FSHD1 deltoid, bicep and TA over a time course of differentiation. We find that TA and quadricep retain methylation and expression differences in transcription factors that are key to muscle group specification during embryogenesis. FSHD2 patients have differences in DNA methylation and expression related to SMCHD1 mutations and FGF signaling. Genes induced specifically in FSHD are more highly expressed in commonly affected muscle groups. We find a set of genes that distinguish more susceptible muscle groups including development-associated TFs and genes involved in WNT signaling. Adult muscle groups therefore retain transcriptional and DNA methylation differences associated with development, which may contribute to susceptibility in FSHD.
Adeno-associated virus (AAV) reduces cortical dendritic complexity in a TLR9-dependent manner
Authors: Suriano Christos M. , Verpeut Jessica L. , Kumar Neerav , Ma Jie , Jung Caroline , Boulanger Lisa M.
Published: September 2021

Recombinant adeno-associated viruses (AAVs) allow rapid and efficient gene delivery in the nervous system. AAVs are widely used in research and are the basis of multiple FDA-approved gene therapies. Here, we find that the immune response to AAV’s genome reduces dendritic complexity in mammalian cortex. Dendritic loss associated with AAV-mediated gene delivery occurs at experimentally-relevant titers, cannot be explained by responses to transgene expression or surgery, and is not restricted to a particular capsid serotype, encoded transgene, promoter, or production facility. AAV-associated dendritic loss is accompanied by a decrease in the frequency and amplitude of miniature excitatory postsynaptic currents (mEPSCs) and upregulation of immune molecules that can limit dendritic complexity and synaptic transmission. Blocking detection of unmethylated CpG-rich DNA via Toll-like receptor 9 (TLR9) protects dendritic complexity, suggesting that immunodetection of a core feature of the AAV genome triggers dendritic loss. These results reveal previously unsuspected impacts of AAV on neuronal structure and function and identify TLR9 inhibitors as important tools to improve the safety and efficacy of AAV-mediated gene delivery in the nervous system.
Osteoblasts pattern endothelium and somatosensory axons during zebrafish caudal fin organogenesis
Authors: Bump Rosalind G. , Goo Camille E. A. , Horton Emma C. , Rasmussen Jeffrey P.
Published: September 2021

Skeletal elements frequently associate with vasculature and somatosensory nerves, which regulate bone development and homeostasis. However, the deep, internal location of bones in many vertebrates has limited in vivo exploration of the neurovascular-bone relationship. Here, we use the zebrafish caudal fin, an optically accessible organ formed of repeating bony ray skeletal units, to determine the cellular relationship between nerves, bones, and endothelium. In adults, we establish the presence of somatosensory axons running through the inside of the bony fin rays, juxtaposed with osteoblasts on the inner hemiray surface. During development, we show the caudal fin progresses through sequential stages of endothelial plexus formation, bony ray addition, ray innervation, and endothelial remodeling. Surprisingly, the initial stages of fin morphogenesis proceed normally in animals lacking either fin endothelium or somatosensory nerves. Instead, we find that sp7+ osteoblasts are required for endothelial remodeling and somatosensory axon innervation in the developing fin. Overall, this study demonstrates that the proximal neurovascular-bone relationship in the adult caudal fin is established during fin organogenesis and suggests that ray-associated osteoblasts pattern axons and endothelium.

Summary statement

Analysis of cellular interdependence during caudal fin development reveals roles for osteoblasts in patterning endothelium and somatosensory axon innervation.
Regulation of Blos1 by IRE1 prevents the accumulation of Huntingtin protein aggregates
Authors: Bae Donghwi , Jones Rachel Elizabeth , Piscopo Katherine M. , Tyagi Mitali , Shepherd Jason D. , Hollien Julie
Published: September 2021

Huntington’s disease is characterized by accumulation of the aggregation-prone mutant Huntingtin (mHTT) protein. Here, we show that expression of mHTT in mouse cultured cells activates IRE1, the transmembrane sensor of stress in the endoplasmic reticulum, leading to degradation of the Blos1 mRNA and repositioning of lysosomes and late endosomes toward the microtubule organizing center. Overriding Blos1 degradation results in excessive accumulation of mHTT aggregates in both cultured cells and primary neurons. Although mHTT is degraded by macroautophagy when highly expressed, we show that prior to the formation of large aggregates, mHTT is degraded via an ESCRT-dependent, macroautophagy-independent pathway consistent with endosomal microautophagy. This pathway is enhanced by Blos1 degradation and appears to protect cells from a toxic, less aggregated form of mHTT.

Condensed title

Blos1 regulation protects from Huntingtin aggregation

Short summary

Here the authors demonstrate that the regulation of Blos1 by the unfolded protein response prevents the excessive accumulation of Huntingtin, the protein that underlies Huntington’s disease. This pathway involves the macroautophagy-independent degradation of Huntingtin prior to its forming large aggregates.
The Mediating Role of SES on the Relationship between Pregnancy History and Later Life Cognition
Authors: Giudicessi Averi J. , Saelzler Ursula G. , Shadyab Aladdin H. , Posis Alexander Ivan B. , Sundermann Erin , Banks Sarah J. , Panizzon Matthew S.
Published: September 2021

Objective

The association of pregnancy with later life cognition is not well understood. Few studies address the potential confounding role of socioeconomic factors on this relationship. We examined whether pregnancy was associated with cognitive function in a large, population-based sample of post-menopausal women and the potential mediating effects of education level and federal income-to-poverty ratio (PIR) on this relationship.

Methods

Participants were 1,016 post-menopausal women from the National Health and Nutrition Examination Survey (NHANES). We utilized data from two study waves between years 2011-2014. Cognitive functioning was evaluated by: Digit Symbol Substitution Test (DSST), Animal Fluency (AF), Consortium to Establish a Registry for Alzheimer’s Disease CERAD word learning task (CERAD-WL) and CERAD delayed recall (CERAD-DR). Lifetime education level and federal income-to-poverty ratio (PIR) were examined as mediating factors. Regression models were used to examine the relationship between number of term pregnancies and incomplete pregnancies and cognitive performance.

Results

A greater number of term pregnancies was related to worse performance on the DSST (p < .001), CERAD-DR (p < .007), and AF (p < .03). Conversely, greater incomplete pregnancies related to better CERAD-DR performance (p < .03). Significant associations between term pregnancies and cognitive scores were mediated by PIR but not education level.

Conclusions

Higher number of term pregnancies was associated with worse cognitive performance, whereas higher number of incomplete pregnancies was associated with better cognitive performance. Results indicate the necessity to consider SES factors when studying the relationship between pregnancy and cognition.