bluuebunny/crossref_metadata_2025 huggingface dataset:
Distribution and regulatory roles of oxidized 5-methylcytosines in DNA and RNA of the basidiomycete fungi
Laccaria bicolor
and
Coprinopsis cinerea
Authors: Ličytė Janina , Kvederavičiūtė Kotryna , Rukšėnaitė Audronė , Godliauskaitė Eglė , Gibas Povilas , Tomkutė Vita , Petraitytė Gražina , Masevičius Viktoras , Klimašauskas Saulius , Kriukienė Edita
Published: March 2022

The formation of three oxidative DNA 5-methylcytosine (5mC) modifications (oxi-mCs)—5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC)—by the TET/JBP family of dioxygenases prompted intensive studies of their functional roles in mammalian cells. However, the functional interplay of these less abundant modified nucleotides in other eukaryotic lineages remains poorly understood. We carried out a systematic study of the content and distribution of oxi-mCs in the DNA and RNA of the basidiomycetes
Laccaria bicolor
and
Coprinopsis cinerea,
which are established models to study DNA methylation and developmental and symbiotic processes. Quantitative liquid chromatography–tandem mass spectrometry revealed persistent but uneven occurrences of 5hmC, 5fC and 5caC in the DNA and RNA of the two organisms, which could be upregulated by vitamin C. 5caC in RNA (5carC) was predominantly found in non-ribosomal RNA, which potentially includes non-coding, messenger and small RNA species. Genome-wide mapping of 5hmC and 5fC using the single CG analysis techniques hmTOP-seq and foTOP-seq pointed at involvement of oxi-mCs in the regulation of gene expression and silencing of transposable elements. The implicated diverse roles of 5mC and oxi-mCs in the two fungi highlight the epigenetic importance of the latter modifications, which are often neglected in standard whole-genome bisulfite analyses.
Modelling T-cell immunity against hepatitis C virus with liver organoids in a microfluidic coculture system
Authors: Natarajan Vaishaali , Simoneau Camille R. , Erickson Ann L. , Meyers Nathan L. , Baron Jody L. , Cooper Stewart , McDevitt Todd C. , Ott Melanie
Published: March 2022

Hepatitis C virus (HCV) remains a global public health challenge with an estimated 71 million people chronically infected, with surges in new cases and no effective vaccine. New methods are needed to study the human immune response to HCV since
in vivo
animal models are limited and
in vitro
cancer cell models often show dysregulated immune and proliferative responses. Here, we developed a CD8
+
T cell and adult stem cell liver organoid system using a microfluidic chip to coculture 3D human liver organoids embedded in extracellular matrix with HLA-matched primary human T cells in suspension. We then employed automated phase contrast and immunofluorescence imaging to monitor T cell invasion and morphological changes in the liver organoids. This microfluidic coculture system supports targeted killing of liver organoids when pulsed with a peptide specific for HCV non-structural protein 3 (NS3) (KLVALGINAV) in the presence of patient-derived CD8
+
T cells specific for KLVALGINAV. This demonstrates the novel potential of the coculture system to molecularly study adaptive immune responses to HCV in an
in vitro
setting using primary human cells.
Digging deeper into colonial palaeontological practices in modern day Mexico and Brazil
Authors: Cisneros Juan Carlos , Raja Nussaïbah B. , Ghilardi Aline M. , Dunne Emma M. , Pinheiro Felipe L. , Regalado Fernández Omar Rafael , Sales Marcos A. F. , Rodríguez-de la Rosa Rubén A. , Miranda-Martínez Adriana Y. , González-Mora Sergio , Bantim Renan A. M. , de Lima Flaviana J. , Pardo Jason D.
Published: March 2022

Scientific practices stemming from colonialism, whereby middle- and low-income countries supply data for high-income countries and the contributions of local expertise are devalued, are still prevalent today in the field of palaeontology. In response to these unjust practices, countries such as Mexico and Brazil adopted protective laws and regulations during the twentieth century to preserve their palaeontological heritage. However, scientific colonialism is still reflected in many publications describing fossil specimens recovered from these countries. Here, we present examples of ‘palaeontological colonialism’ from publications on Jurassic–Cretaceous fossils from NE Mexico and NE Brazil spanning the last three decades. Common issues that we identified in these publications are the absence of both fieldwork and export permit declarations and the lack of local experts among authorships. In Mexico, access to many fossil specimens is restricted on account of these specimens being housed in private collections, whereas a high number of studies on Brazilian fossils are based on specimens illegally reposited in foreign collections, particularly in Germany and Japan. Finally, we outline and discuss the wider academic and social impacts of these research practices, and propose exhaustive recommendations to scientists, journals, museums, research institutions and government and funding agencies in order to overcome these practices.
Environmental drivers of population-level variation in the migratory and diving ontogeny of an Arctic top predator
Authors: Grecian W. James , Stenson Garry B. , Biuw Martin , Boehme Lars , Folkow Lars P. , Goulet Pierre J. , Jonsen Ian D. , Malde Aleksander , Nordøy Erling S. , Rosing-Asvid Aqqalu , Smout Sophie
Published: March 2022

The development of migratory strategies that enable juveniles to survive to sexual maturity is critical for species that exploit seasonal niches. For animals that forage via breath-hold diving, this requires a combination of both physiological and foraging skill development. Here, we assess how migratory and dive behaviour develop over the first year of life for a migratory Arctic top predator, the harp seal
Pagophilus groenlandicus
, tracked using animal-borne satellite relay data loggers. We reveal similarities in migratory movements and differences in diving behaviour between 38 juveniles tracked from the Greenland Sea and Northwest Atlantic breeding populations. In both regions, periods of resident and transitory behaviour during migration were associated with proxies for food availability: sea ice concentration and bathymetric depth. However, while ontogenetic development of dive behaviour was similar for both populations of juveniles over the first 25 days, after this time Greenland Sea animals performed shorter and shallower dives and were more closely associated with sea ice than Northwest Atlantic animals. Together, these results highlight the role of both intrinsic and extrinsic factors in shaping early life behaviour. Variation in the environmental conditions experienced during early life may shape how different populations respond to the rapid changes occurring in the Arctic ocean ecosystem.
Synthesis of novel silica encapsulated spiropyran-based thermochromic materials
Authors: Iqbal Anila , Iqbal Ghazala , Umar Muhammad Naveed , ur Rashid Haroon , Khan Sher Wali
Published: March 2022

A series of novel spiropyrans were synthesized through the condensation of substituted 3,3-dimethyl-2-methyleneindoline with different nitro-substituted
o
-hydroxy aromatic aldehydes. Indoles were initially substituted with a variety of alkanes and esters moieties. The substituted 3,3-dimethyl-2-methyleneindoline was then reacted with nitro-substituted
o
-hydroxy aromatic aldehydes to yield the respective spiropyrans. The synthesized novel spiropyrans were encapsulated in silica nano-shells to protect them from the effect of moisture and pH. The thermochromic behaviour of novel spiropyrans was studied by UV-visible spectroscopy. The thermally induced isomerization of spiropyran derivatives was carried out in a water/ethanol mixture. The thermal isomerization of spiro-heterocyclic (colourless form) to merocyanine (MC) (coloured form) was a discontinuous process and was observed in a temperature range of 5–60°C via UV-visible spectrometer. The absorption process occurs reversibly regardless of the heating/cooling sequence. The spiropyran derivatives, therefore, have a potential application for colorimetric temperature indication.
Environmental determinants predicting population vulnerability to high yellow fever incidence
Authors: Servadio Joseph L. , Muñoz-Zanzi Claudia , Convertino Matteo
Published: March 2022

Yellow fever (YF) is an endemic mosquito-borne disease in Brazil, though many locations have not observed cases in recent decades. Some locations with low disease burden may resemble locations with higher disease burden through environmental and ecohydrological characteristics, which are known to impact YF burden, motivating increased or continued prevention measures such as vaccination, mosquito control or surveillance. This study aimed to use environmental characteristics to estimate vulnerability to observing high YF burden among all Brazilian municipalities. Vulnerability was defined in three categories based on yearly incidence between 2000 and 2017: minimal, low and high vulnerability. A cumulative logit model was fit to these categories using environmental and ecohydrological predictors, selecting those that provided the most accurate model fit. Per cent of days with precipitation, mean temperature, biome, population density, elevation, vegetation and nearby disease occurrence were included in best-fitting models. Model results were applied to estimate vulnerability nationwide. Municipalities with highest probability of observing high vulnerability was found in the North and Central-West (2000–2016) as well as the Southeast (2017) regions. Results of this study serve to identify specific locations to prioritize new or ongoing surveillance and prevention of YF based on underlying ecohydrological conditions.
Prey encounters and spatial memory influence use of foraging patches in a marine central place forager
Authors: Iorio-Merlo Virginia , Graham Isla M. , Hewitt Rebecca C. , Aarts Geert , Pirotta Enrico , Hastie Gordon D. , Thompson Paul M.
Published: March 2022

Given the patchiness and long-term predictability of marine resources, memory of high-quality foraging grounds is expected to provide fitness advantages for central place foragers. However, it remains challenging to characterize how marine predators integrate memory with recent prey encounters to adjust fine-scale movement and use of foraging patches. Here, we used two months of movement data from harbour seals (
Phoca vitulina
) to quantify the repeatability in foraging patches as a proxy for memory. We then integrated these data into analyses of fine-scale movement and underwater behaviour to test how both spatial memory and prey encounter rates influenced the seals' area-restricted search (ARS) behaviour. Specifically, we used one month's GPS data from 29 individuals to build spatial memory maps of searched areas and archived accelerometery data from a subset of five individuals to detect prey catch attempts, a proxy for prey encounters. Individuals were highly consistent in the areas they visited over two consecutive months. Hidden Markov models showed that both spatial memory and prey encounters increased the probability of seals initiating ARS. These results provide evidence that predators use memory to adjust their fine-scale movement, and this ability should be accounted for in movement models.
Pichia bovicola sp. nov., a yeast species associated with small-intestinal content of cattle
Authors: Angchuan Jirameth , Sakpuntoon Varunya , Limtong Savitree , Srisuk Nantana
Published: March 2022

Three yeast strains, DMKU-MP6-4T, DMKU-MP2-6 and DMKU-MP5-1, were isolated from the small-intestinal content or Pia of cattle in Thailand during the investigation of yeast diversity in this habitat. According to the D1/D2 domain of the large subunit (LSU) rRNA gene and internal transcribed spacer (ITS) region sequence analysis, these strains represent a novel yeast species in the genus Pichia. The species produced one to four ascospores per ascus with spherical to ellipsoidal shape and heterogenous in terms of size. These three strains were identical and differed from their closely related species, Pichia exigua NRRL Y-10920T by 2% (six nucleotide substitutions and five gaps) in the D1/D2 domain of the large subunit rRNA gene, while ITS region sequences differed by 3.1% (16 nucleotide substitutions and 27 gaps), 3.7% (19 nucleotide substitutions and 28 gaps) and 3.1% (16 nucleotide substitutions and 27 gaps) for DMKU-MP6-4T, DMKU-MP2-6 and DMKU-MP5-1, respectively. The name, Pichia bovicola, is proposed to accommodate these species. The holotype is DMKU-MP6-4T (TBRC 15616T=PYCC 8905T).
Assessing the heterogeneity in the transmission of infectious diseases from time series of epidemiological data
Authors: Schneckenreither Günter , Herrmann Lukas , Reisenhofer Rafael , Popper Nikolas , Grohs Philipp
Published: March 2022

Structural features and the heterogeneity of disease transmissions play an essential role in the dynamics of epidemic spread. But these aspects can not completely be assessed from aggregate data or macroscopic indicators such as the effective reproduction number. We propose an index of effective aggregate dispersion (EffDI) that indicates the significance of infection clusters and superspreading events in the progression of outbreaks by carefully measuring the level of stochasticity in time series of reported case numbers. This allows to detect the transition from predominantly clustered spreading to a diffusive regime with diminishing significance of singular clusters, which can be decisive for the future progression of outbreaks and relevant in the planning of containment measures. We evaluate EffDI for SARS-CoV-2 case data in different countries and compare the results with a quantifier for the socio-demographic heterogeneity in disease transmissions in a case study to substantiate that EffDI qualifies as a measure for the heterogeneity in transmission dynamics.
Healthcare services access, use, and barriers among migrants in Europe: a systematic review
Authors: Galanis Petros , Spyros Koureas , Siskou Olga , Konstantakopoulou Olympia , Angelopoulos Georgios , Kaitelidou Daphne
Published: March 2022

Background

The issue of migrants health and access to health services is dynamic and complex posing a challenge to health systems worldwide.

Aim

To investigate migrants’ access to health services in European countries, the use of health services by migrants and the barriers encountered by migrants in the use of health services.

Material and methods

The search was conducted in January 2022 in five databases; PubMed, Medline, Web of science, Scopus and Cinahl. We used the following keywords: migrants, immigrants, use, access, utilization, healthcare services, services, needs, health, difficulties, barriers. The inclusion criteria were the following: (a) the studies investigated the access of migrants to health services, the use of health services by migrants and the barriers encountered by migrants in using health services. (b) migrants self-assessed access, use and barriers. (c) studies were conducted in European countries. (d) studies included adult migrants. (e) the language of articles was English.

Results

Sixty-five studies were met our inclusion criteria. among studies, 89.2% were quantitative and 11.8% were qualitative. All quantitative studies were cross-sectional. for data collection, 58.5% of studies used questionnaires and 30.8% used historical files. Also, personal interviews were performed in 9.2% of studies and focus groups in 1.5% of studies. in our studies, 73.8% of natives stated that they had better access to health services and used health services better than migrants, while 26.2% found that migrants stated that they had better access to health services and used health services better. The most common barriers were the following: inability to understand the language and communicate, lack of insurance, lack of information and knowledge, lack of family support, low educational level, short duration of stay in the country of migration, low income, lack of a family doctor and high costs.

Conclusions

Migrants face several barriers both in accessing and using health services in Europe. Intensive efforts are needed to increase migrants’ knowledge, implement culturally sensitive interventions in migrant communities and better inform healthcare professionals so that they can approach migrants more effectively.
A pleiotropic flowering time QTL exhibits gene-by-environmental interaction for fitness in a perennial grass
Authors: Weng Xiaoyu , Haque Taslima , Zhang Li , Razzaque Samsad , Lovell John T , Palacio-Mejía Juan Diego , Duberney Perla , Lloyd-Reilley John , Bonnette Jason , Juenger Thomas E
Published: March 2022

Flowering time is crucial for wild plant populations to adapt to their local environments. Although the genetic basis of flowering variation has been studied in many plant species, its mechanisms in non-model organisms and its adaptive value in the field are still poorly understood. Here, we report new insights into the genetic basis of flowering time and its effect on fitness inPanicum hallii, a native perennial grass. We conducted genetic mapping in populations derived from representative inland and coastal ecotypes to identify flowering time QTL and loci exhibited extensive QTL-by-environment interactions. Patterns of segregation within recombinant hybrids provide strong support for directional selection driving ecotypic divergence in flowering time. A major QTL on chromosome 5 (q-FT5) was detected in all experiments and is a key locus controlling flowering variation. Fine-mapping and expression studies identified aFLOWERING LOCUS Torthologue,FT-like 9(PhFTL9), as the candidate underlyingq-FT5. We used reciprocal transplant experiment to test for global local adaptation and the specific impact ofq-FT5on performance. We did not observe local adaptation in terms of fitness tradeoffs when contrasting ecotypes in home versus away habitats. However, we observed that the coastal allele ofq-FT5conferred a fitness advantage only in its local habitat but not at the inland site. Sequence analysis of thePhFTL9promoter identified ecotypic specificcis-element variation associated with environmental responsiveness. Together, our findings demonstrate the genetic basis of flowering variation in a perennial grass and provide evidence for conditional neutrality underlying flowering divergence.
Whole genome regulatory effect ofMoISW2and consequences for the evolution of the rice plant pathogenic fungusMagnaporthe oryzae
Authors: Pei Mengtian , Abubakar Yakubu Saddeeq , Ali Hina , Lin Lianyu , Dou Xianying , Lu Guodong , Wang Zonghua , Olsson Stefan , Li Ya
Published: March 2022

Isw2 proteins are conserved in eukaryotes and are known to bind to DNA and dynamically influence local chromosome condensation close to their DNA binding site in an ATP-dependent manner making genes close to the binding sites more accessible for transcription and repression. A putativeMoISW2gene was deleted with large effects on plant pathogenicity as a result. The gene was complemented and a ChIP-sec was performed to identify binding sites. RNAsec showed effects on the overall regulation of genes along the chromosomes for mutant and background strains and this was compared with RNAseq from 55 downloaded RNA-seq datasets from the same strain and found similar. MoIsw2 binding and activities create genomic regions affected by MoIsw2 with high gene expression variability close to the MoIsw2 binding sites while surrounding regions have lower gene expression variability. The genes affected by the MoIsw2 activity are niche-determinant genes (secreted proteins, secondary metabolites and stress-coping genes) and avirulence genes. We further show that MoIsw2 binding sites with the DNA binding motifs coincide with known transposable elements (TE) making it likely that TE-transposition at the binding sites can affect the transcription profile ofM. oryzein a strain-specific manner. We conclude that MoIsw2 is a likely candidate for a master regulator, regulating the dynamic balance between biomass growth genes (like housekeeping genes) and nich-determinant genes important for ecological fitness. Stress-induced TE transposition is together with MoIsw2 activity a likely mechanism creating more mutations and faster evolution of the niche-determinant genes than for housekeeping genes.
Local Subspace Pruning (LSP) for Multichannel Data Denoising
Authors: de Cheveigné Alain
Published: March 2022

This paper proposes a simple algorithm to remove noise and artifact from multichannel data. Data are processed trial by trial: for each trial the covariance matrix of the trial is diagonalized together with that of the full data to reveal the subspace that is – locally – most eccentric relative to other trials. That subspace is then projected out from the data of that trial. This algorithm addresses a fundamental limitation of standard linear analysis methods (e.g. ICA) that assume that brain and artifact are linearly separable within the data. That assumption fails if there are more sources, including noise and brain sources, than data channels. The algorithm captitalizes on the fact that, if enough of those sources are temporally sparse, linear separation may succeed locally in time. The paper explains the rationale, describes the algorithm, and evaluates the outcome using synthetic and real brain data.
Nrf2 promotes thyroid development and hormone synthesis
Authors: Pierre Gillotay , Mirian Romitti , Benjamin Dassy , Benoit Haerlingen , Meghna Parakkal Shankar , Barbara Faria Fonseca , Panos Ziros G. , Sumeet Pal Singh , Gerasimos Sykiotis P. , Sabine Costagliola
Published: March 2022

In all vertebrates, the function of the thyroid gland is to capture iodide to synthesize hormones that act on almost all tissues and are essential for normal growth and metabolism. Thyroid hormone production is a multistep process that ultimately leads to the coupling of iodine to thyroglobulin, the matrix glycoprotein of hormone synthesis. This coupling is dependent on H2O2, the accumulation of which in thyroid tissue, a true iodine trap, causes a basal level of oxidative stress higher than in other tissues, which, if left unchecked, leads to cellular damage. The thyroid has efficient antioxidant and detoxifying enzymes that help it resist H202-induced oxidative stress and maintain the homeostasis necessary for hormone synthesis. By regulating the expression of genes involved in cellular detoxification processes, the transcription factor NRF2 acts as a master regulator of the cellular defense system against oxidative stress. Using zebrafish embryos and mouse thyroid organoids, we show here that direct control of thyroglobulin expression by NRF2 is an evolutionarily conserved chore mechanism in vertebrates to complete the necessary molecular defense arsenal against oxidative stress in thyroid tissue.
Interactions of C. elegans β-tubulins with the microtubule inhibitor albendazole
Authors: Pallotto Linda M. , Dilks Clayton M. , Park Ye-Jean , Smit Ryan B. , Lu Brian , Gopalakrishnan Chandrasekhar , Gilleard John S. , Andersen Erik C. , Mains Paul E.
Published: March 2022

Parasitic nematodes are major human and agricultural pests, and benzimidazoles are amongst the most important broad spectrum anthelmintic drug class used for their control. Benzimidazole resistance is now widespread in many species of parasitic nematodes in livestock globally and an emerging concern for the sustainable control of human soil transmitted helminths. β-tubulin is the major benzimidazole target, although other genes may influence resistance. Among the six C. elegans β-tubulin genes, loss of ben-1 causes resistance without other apparent defects. Here, we explored the genetics of C. elegans β-tubulin genes in relation to the response to the benzimidazole derivative albendazole. The most highly expressed β-tubulin isotypes, encoded by tbb-1 and tbb-2, were known to be redundant with each other for viability, and their products are predicted not to bind benzimidazoles. We found that tbb-2 mutants, and to a lesser extent tbb-1 mutants, were hypersensitive to albendazole. The double mutant tbb-2 ben-1 is uncoordinated and dumpy, resembling the wild type exposed to albendazole, but the tbb-1 ben-1 double mutant did not show the same phenotype. These results suggest that tbb-2 is a modifier of ABZ sensitivity. To better understand how BEN-1 mutates to cause benzimidazole resistance, we isolated mutants resistant to albendazole and found that 15 of 16 mutations occurred in ben-1. Mutations ranged from likely nulls to hypomorphs, and several corresponded to residues that cause resistance in other organisms. Null alleles of ben-1 are albendazole-resistant and BEN-1 shows high sequence identity with tubulins from other organisms, suggesting that many amino acid changes could cause resistance. However, our results suggest that missense mutations conferring resistance are not evenly distributed across all possible conserved sites. Independent of their roles in benzimidazole resistance, tbb-1 and tbb-2 may have specialized functions as null mutants of tbb-1 or tbb-2 were cold or heat sensitive, respectively.
Cross-cultural adaptation and validation of the “COVID Stress Scales” in Greek
Authors: Galanis Petros , Vraka Irene , Katsiroumpa Aglaia , Konstantakopoulou Olympia , Siskou Olga , Zogaki Eleftheria , Kaitelidou Daphne
Published: March 2022

Background

During the COVID-19 pandemic, several instruments were developed to measure the psychological impact of COVID-19, such as fear, anxiety, post-traumatic stress, phobia, etc.

Objective

To adapt cross-cultural and validate the “COVID Stress Scales” in Greek.

Methods

We conducted a cross-sectional study with 200 participants between November 2021 to February 2022. All participants were adults, and a convenience sample was obtained. We applied the forward-backward translation method to create a Greek version of the “COVID Stress Scales”. We assessed reliability of the questionnaire with test-retest method in a 10-day window, and we assessed validity of the questionnaire with exploratory factor analysis.

Results

Our five-factor model explained 72% of the variance and totally confirmed the factors of the initial “COVID Stress Scales”. In particular, we found the following five factors: (a) COVID-19 danger and contamination (eleven items), (b) COVID-19 socioeconomic consequences (six items), (c) COVID-19 xenophobia (six items), (d) COVID-19 traumatic stress (six items), and (e) COVID-19 compulsive checking (six items). Cronbach’s coefficients alpha for the five factors that emerged from the exploratory factor analysis were greater than 0.89 indicating excellent internal reliability.

Conclusions

We found that the “COVID Stress Scales” is a reliable and valid tool to measure stress due to the COVID-19 in the Greek population.
Person-specific Characteristics of People with Low Back Pain Moderate the Preferred Movement Pattern within Motor Skill Training and Strength and Flexibility Exercise
Authors: Hooker Quenten L. , Dillen Linda R. van
Published: March 2022

Background

People with chronic low back pain (LBP) display an altered movement pattern where the lumbar spine moves more readily into its available range of motion relative to other joints when performing a movement. Recently a randomized controlled trial was completed to compare the effects of motor skill training (MST) to strength and flexibility exercise (SFE). MST improved the altered pattern to a greater extent than SFE. However, there was substantial variability in the baseline and the change over time in the pattern. Understanding factors that influence this variability may ultimately be used to better target treatment strategies to the person.

Objective

Examine if gender, age, LBP duration, and the movement pattern at baseline moderate the baseline movement pattern and the change over time in the pattern within MST and SFE. Design: Secondary analysis of kinematic data from a single-blind, randomized controlled clinical trial.

Setting

Institutional

Patients

154 patients with chronic LBP.

Interventions

Motor skill training and strength and flexibility exercise.

Main outcome measures

lumbar contribution (LC) to total movement.

Results

There was not a significant difference in baseline LC between MST and SFE (β=-2.39, CI=[-7.74, 2.96], p=0.38). SFE did not change LC over time (β=-0.11, CI=[-0.47, 0.24], p=0.53). However, there was a significant change over time in LC within MST (β=-2.13, CI=[-2.54, -1.48], p<0.001). Irrespective of treatment group, there was a trend for gender (β=-5.29, CI=[-10.34, 0.30], p=0.05) and age (β=-0.22, CI=[-0.46, 0.00], p=0.05) to moderate baseline LC. Age (β=0.01, CI=[0.00, 0.02], p = 0.04) and baseline LC (β=-0.07, CI=[-0.10, -0.04], p<0.01) were associated with the change over time in LC within MST only.

Conclusions

Person-specific characteristics moderate the baseline altered movement pattern within MST and SFE, as well as the change over time in the pattern within MST.
Government restriction efficiency on curbing COVID-19 pandemic transmission in Western Europe
Authors: Lolli Simone , Vivone Gemine
Published: March 2022

In this article we assess the effectiveness of the restrictions, implemented at government level, to curb the first wave of the COVID-19 outbreak (January-May 2020) in seven European countries. The analysis put in evidence a strong correlation (correlation coefficient greater than 0.85) between one of the statistical parameters of the distribution representing the temporal evolution of the weekly number of patients admitted into the Intensive Cure Unit (ICU), i.e., the skewness, and the Stringency Index, an aggregate synthetic variable that reflects the level of implemented restrictions by a specific country on a scale between 0 (no restrictions) and 100 (full lockdown). Then, to assess if the skewness is consistent in effectively reflecting the applied restrictions, we computed the skewness for non-Covid flu outbreaks during four years from 2014-2015 to 2018-2019 and Covid-19 outbreak, where no restrictions were applied in Italy. The results highlight a significant difference between the values of the skewness for the normal flu with respect to the COVID-19 outbreak. This large difference put in evidence that the implemented restrictions modify the skewness of the ICU hospitalized patient number distribution. The skewness then can be used as a valid indicator to assess if the restriction had any effect on pandemic transmission and can be used as a support for decision makers.
Unquantifiably low aldosterone concentrations are prevalent in hospitalised COVID-19 patients but may not be revealed by chemiluminescent immunoassay
Authors: Wiegand Martin , Halsall David J. , Cowan Sarah L. , Taylor Kevin , Goudie Robert J. B. , Preller Jacobus , Gurnell Mark
Published: March 2022

Objective

Previous studies have reported conflicting findings regarding aldosterone levels in patients hospitalised with COVID-19. We therefore used the gold-standard technique of liquid chromatography tandem mass-spectrometry (LCMSMS) to address this uncertainty.

Design

All patients admitted to Cambridge University Hospitals with COVID-19 between March 10, 2020 and May 13, 2021, and in whom a stored blood sample was available for analysis, were eligible for inclusion.

Methods

Aldosterone was measured by LCMSMS and by immunoassay; cortisol and renin were determined by immunoassay.

Results

Using LCMSMS, aldosterone was below the limit of detection (<70 pmol/L) in 74 (58.7%) patients. Importantly, this finding was discordant with results obtained using a commonly employed clinical immunoassay (Liaison Diasorin®), which over-estimated aldosterone compared to the LCMSMS assay (intercept 14.1 [95% CI -34.4 to 54.1] + slope 3.16 [95% CI 2.09 to 4.15] pmol/L). The magnitude of this discrepancy did not clearly correlate with markers of kidney or liver function. Solvent extraction prior to immunoassay improved the agreement between methods (intercept -14.9 [95% CI -31.9 to -4.3] and slope 1.0 [95% CI 0.89 to 1.02] pmol/L) suggesting the presence of a water-soluble metabolite causing interference in the direct immunoassay. We also replicated a previous finding that blood cortisol concentrations were often increased, with increased mortality in the group with serum cortisol levels >744 nmol/L (p=0.005).

Conclusion

When measured by LCMSMS, aldosterone was found to be profoundly low in a significant proportion of patients with COVID-19 at the time of hospital admission. This has likely not been detected previously due to high levels of interference with immunoassays in patients with COVID-19, and this merits further prospective investigation.
Multi-ancestry meta-analysis identifies 2 novel loci associated with ischemic stroke and reveals heterogeneity of effects between sexes and ancestries
Authors: Surakka Ida , Wu Kuan-Han , Hornsby Whitney , Wolford Brooke N. , Shen Fred , Zhou Wei , Huffman Jennifer E. , Pandit Anita , Hu Yao , Brumpton Ben , Skogholt Anne Heidi , Gabrielsen Maiken E. , Walters Robin G. ,   The TOPMed Stroke Working Group, Million Veteran Program (MVP), Hveem Kristian , Kooperberg Charles , Zöllner Sebastian , Wilson Peter W.F. , Sutton Nadia R. , Daly Mark J. , Neale Benjamin M. , Willer Cristen J.
Published: March 2022

Cerebrovascular accident (stroke) is the second leading cause of death and disability worldwide. Stroke prevalence varies by sex and ancestry, which could be due to genetic heterogeneity between subgroups. We performed a genome-wide meta-analysis of 16 biobanks across multiple ancestries to study the genetic contributions underlying ischemic stroke (60,176 cases, 1,310,725 controls) as part of the Global Biobank Meta-analysis Initiative (GBMI). Two novel loci associated ischemic stroke with plausible candidate genes, FGF5 and CENPQ/MUT, were identified after replication in four additional datasets. One locus showed significant ancestry heterogeneity (PDE3A) and two loci showed significant sex-heterogeneity (SH3PXD2A and ALDH2). The ALDH2 locus had a male-specific association for stroke in GBMI (P-value males = 1.67e-24, P-value females = 0.126). To test whether we would see a difference in the predictive power of sex-specific polygenic risk scores (PRSs), we compared the C-indexes for sex-specific and sex-combined PRSs in HUNT dataset. A sex-combined PRS was more successful at predicting stroke cases than a sex-specific PRS, most likely due to more stable effect estimates from the sex-combined summary-statistics. These approaches can be applied to further unravel the genetic underpinnings of stroke and other complex diseases.
A causal inference approach for estimating effects of non-pharmaceutical interventions during Covid-19 pandemic
Authors: Barros Vesna , Manes Itay , Akinwande Victor , Cintas Celia , Bar-Shira Osnat , Ozery-Flato Michal , Shimoni Yishai , Rosen-Zvi Michal
Published: March 2022

In response to the outbreak of the coronavirus disease 2019 (Covid-19), governments worldwide have introduced multiple restriction policies, known as non-pharmaceutical interventions (NPIs). However, the relative impact of control measures and the long-term causal contribution of each NPI are still a topic of debate. We present a method to rigorously study the effectiveness of interventions on the rate of the time-varying reproduction number Rtand on human mobility, considered here as a proxy measure of policy adherence and social distancing. We frame our model using a causal inference approach to quantify the impact of five governmental interventions introduced until June 2020 to control the outbreak in 113 countries: confinement, school closure, mask wearing, cultural closure, and work restrictions. Our results indicate that mobility changes are more accurately predicted when compared to reproduction number. All NPIs, except for mask wearing, significantly affected human mobility trends. From these, schools and cultural closure mandates showed the largest effect on social distancing. We also found that closing schools, issuing face mask usage, and work-from-home mandates also caused a persistent reduction on Rtafter their initiation, which was not observed with the other social distancing measures. Our results are robust and consistent across different model specifications and can shed more light on the impact of individual NPIs.
C21orf2 mutations found in ALS disrupt primary cilia function
Authors: De Decker Mathias , Zelina Pavol , Moens Thomas G , Eggermont Kristel , Moisse Matthieu , Veldink Jan H. , Van Den Bosch Ludo , Pasterkamp R. Jeroen , Van Damme Philip
Published: March 2022

Amyotrophic lateral sclerosis (ALS) is a devastating progressive neurodegenerative disease that affects 1 in 400 people. Almost 40 genes have been associated with ALS, currently explaining about 15% of the ALS risk. These genes tend to cluster in certain disease pathways such as protein quality control, RNA metabolism and axonal function. Despite these advances, adequate treatments for ALS patients are still missing. In this study, we investigate the role of a newly discovered ALS gene, C21orf2, in ALS pathology. We show that C21orf2 is localized to the basal body of the primary cilium and plays an important role in ciliogenesis in vitro and in vivo. Knock down of C21orf2 also lowers cilia frequency and length in human iPSC-derived spinal motor neurons (sMNs). Furthermore, we show that intraflagellar transport is impaired, causing primary cilia to fail in transducing extracellular signals essential in the sonic hedgehog pathway. ALS-associated mutations in C21orf2 lead to loss of binding to centrosomal proteins, loss of proper localization at the basal body and hereby prevent C21orf2 from carrying out its normal function in cilia by loss-of-function. Finally, we confirm that sMNs derived from iPSCs from ALS patients with C21orf2 mutations display similar cilia dysfunction and have disturbed sonic hedgehog signaling. Collectively, our data reveal impaired cilia homeostasis as a novel disease mechanism at play in ALS, opening new avenues for further research.
Koisio Technology-Modulated Cell Culture Media can Lead to Markedly Increased Intracellular ATP Levels of Fibroblast Cell Cultures
Authors: Men Yinghui , Zhang Mingchao , Zhu Qi , Ying Weihai
Published: March 2022

It has been reported that Koisio technology-modulated water without external additions of any substances can enter several types of aquaporins with significantly higher rate. In this study we determined the effects of Koisio technology-modulated cell culture media (Koisio media) on the energy state of cells. We found that for the lung fibroblast (L929) cell cultures, Koisio media without any additions of external substances led to approximately an 57% increase in the intracellular ATP levels of the cell cultures at the Cell Passage 6 - 18, compared with regular cell culture media. Seemingly surprisingly, we did not find that Koisio media could significantly affect the mitochondrial membrane potential of the cells, compared with regular cell culture media. Collectively, our study has provided first evidence indicating that Koisio media can lead to remarkable increases in the intracellular ATP levels of the L929 cell cultures, suggesting significant potential of Koisio technology in generating energy-enhancing water. Our finding that Koisio media did not affect the mitochondrial membrane potential has suggested that novel mechanisms may underlie the effects of Koisio media on cellular energy.
ABA-IMPORTING TRANSPORTER 1.1 activity in the endosperm of tomato seeds restrains germination under salinity stress
Authors: Shohat Hagai , Cheriker Hadar , Cohen Amir , Weiss David
Published: March 2022

The plant hormone abscisic acid (ABA) has a central role in the regulation of seed maturation and dormancy. ABA also restrains germination under abiotic-stress conditions. Here we show in tomato (Solanum lycopersicum) that the ABA importer ABA-IMPORTING TRANSPORTER 1.1 (AIT1.1) has a role in radicle emergence following imbibition. AIT1.1 expression was upregulated during imbibition, and CRISPR/Cas9-derived ait1.1 mutant seeds exhibited faster radicle emergence, increased germination and partial resistance to ABA. AIT1.1 was highly expressed in the endosperm, but not in the embryo, and ait1.1 isolated embryos did not show resistance to ABA. On the other hand, loss of AIT1.1 activity promoted the expression of endosperm-weakening related genes, and seed-coat scarification eliminated the promoting effect of ait1.1 on radicle emergence. Therefore, we propose that imbibition-induced AIT1.1 expression in the endosperm, mediates ABA-uptake into endosperm cells to restrain endosperm weakening. While salinity conditions strongly inhibited the wild-type (WT) M82 seed germination, it had much weaker effect on ait1.1 germination. We suggest that this AIT1.1 function was evolved to inhibit germination under unfavorable conditions, such as salinity. Unlike other ABA mutants, ait1.1 exhibited normal seed longevity, and therefore, the ait1.1 allele may have a potential for improving seed germination in crops.
Stage dependent differential influence of metabolic and structural networks on memory across Alzheimer’s disease continuum
Authors: Ng Kok Pin , Qian Xing , Ng Kwun Kei , Ji Fang , Rosa-Neto Pedro , Gauthier Serge , Kandiah Nagaendran , Zhou Juan Helen ,   the Alzheimer’s Disease Neuroimaging Initiative
Published: March 2022

Background

Large-scale neuronal network breakdown underlies memory impairment in Alzheimer’s disease (AD). However, the differential trajectories of the relationships between network organization and memory across pathology and cognitive stages in AD remain elusive. We determined whether and how the influences of individual-level structural and metabolic covariance network integrity on memory varied with amyloid pathology across clinical stages without assuming a constant relationship.

Methods

708 participants from the Alzheimer’s Disease Neuroimaging Initiative were studied. Individual-level structural and metabolic covariance scores in higher-level cognitive and hippocampal networks were derived from magnetic resonance imaging and [18F]fluorodeoxyglucose positron emission tomography using seed-based partial least square analyses. The non-linear associations between network scores and memory across cognitive stages in each pathology group were examined using sparse varying coefficient modelling.

Results

We showed that the associations of memory with structural and metabolic networks in the hippocampal and default mode regions exhibited pathology-dependent differential trajectories across cognitive stages using sparse varying coefficient modelling. In amyloid pathology group, there was an early influence of hippocampal structural network deterioration on memory impairment in the preclinical stage, and a biphasic influence of the angular gyrus-seeded default mode network metabolism on memory in both preclinical and dementia stages. In non-amyloid pathology groups, in contrast, the trajectory of the hippocampus-memory association was opposite and weaker overall, while no metabolism covariance networks were related to memory. Key findings were replicated in a larger cohort of 1280 participants.

Conclusions

Our findings highlight potential windows of early intervention targeting network breakdown at the preclinical AD stage.
Mucin-degrading gut bacteria promote anti-parasitic immunity
Authors: Wolter Mathis , Boudaud Marie , Grant Erica T. , Parrish Amy , De Sciscio Alessandro , Thompson Seona , Gerardy Jean-Jacques , Mittelbronn Michel , Thornton David J. , Macpherson Andrew J. , Grencis Richard K. , Desai Mahesh S.
Published: March 2022

BACKGROUND & AIMS

Host-secreted gastrointestinal mucus plays a key role in the expulsion of intestinal nematode parasites. A balance between mucin secretion by the host and the gut microbial mucin foraging is essential to maintain the intestinal homeostasis, yet little is known about how changes in the mucin–microbiome interactions affect worm infections. Here, we aimed to examine how mucin foraging activity by the microbiome changes the course of parasitic worm infections by modulating the host immune responses.

METHODS

We utilized a gnotobiotic mouse model containing a synthetic human gut microbiota that allows for: 1) a complete removal of the mucin-degrading bacteria from the community; and 2) diet-driven manipulation of the microbiota toward mucin foraging. We infected mice with a murine nematode,Trichuris muris, which resembles human infection withTrichuris trichiura. We examined the temporal dynamics of worm infection including worm burden and the host immune responses, and coupled these readouts to the microbial changes and mucin foraging activity.

RESULTS

The absence of mucin-degrading bacteria in the microbiota enhances susceptibility to parasitic infection—evidenced by higher worm number—by promoting stronger Th1 immune responses. Dietary fiber deprivation increases the microbial mucin-foraging activity, which coincides with a shift in host immune responses from susceptible (chronic, Th1 type) to resistant (acute, Th2 type), thereby promoting worm clearance.

CONCLUSIONS

Our results provide mechanistic insights into how the colonic mucin-degrading bacteria promote anti-parasitic immunity through modulation of the host immune responses. Our study documents a clinically-relevant, novel link in the microbiome–parasite–host immune axis that is useful prerequisite knowledge in managing parasitic infections.
Drastic differential CRISPR-Cas9 induced mutagenesis influenced by DNA methylation and chromatin features
Authors: Weiss Trevor , Crisp Peter A. , Rai Krishan M. , Song Meredith , Springer Nathan M. , Zhang Feng
Published: March 2022

CRISPR-Cas9 mediated genome editing has been widely adopted for basic and applied biological research in eukaryotic systems. While many studies considered DNA sequences of CRISPR target sites as the primary determinant for CRISPR mutagenesis efficiency and mutation profiles, increasing evidence revealed the significant role of chromatin context. Nonetheless, most of the prior studies were limited by the lack of sufficient epigenetic resources and/or by only transiently expressing CRISPR-Cas9 in a short time window. In this study, we leveraged the wealth of high-resolution epigenomic resources in Arabidopsis thaliana to address the impact of chromatin features on CRISPR-Cas9 mutagenesis using stable transgenic plants. Our results indicated that DNA methylation and chromatin features could lead to significant variations in mutagenesis efficiency by up to 250 folds. Low mutagenesis efficiencies were mostly associated with repressive heterochromatic features. This repressive effect appeared to persist through cell divisions but could be alleviated through substantial reduction of DNA methylation at CRISPR target sites. Moreover, specific chromatin features, such as H3K4me1, H3.3, and H3.1, appear to be associated with significant variations in CRISPR-Cas9 mutation profiles reflected by the 1 bp insertion rates. Our findings provided strong evidence that specific chromatin features could have significant and lasting impacts on both CRISPR-Cas9 mutagenesis efficiency and DNA double strand break repair outcomes.