bluuebunny/crossref_metadata_2025 huggingface dataset:
Hierarchical unimodal processing within the primary somatosensory cortex during a bimodal detection task
Authors: Parra Sergio , Diaz Héctor , Zainos Antonio , Alvarez Manuel , Zizumbo Jerónimo , Pujalte Sebastián , Bayones Lucas , Romo Ranulfo , Rossi-Pool Román
Published: August 2022

Where and how in the brain do neurons process more than one sensory modality? To answer these questions, scientists have generated a wide variety of studies at distinct space-time scales in different animal models, and often shown contradictory conclusions. Some conclude that this process occurs in early sensory cortices, but others that this occurs in areas central to sensory cortices. Here, we sought to determine whether sensory neurons process and encode physical stimulus properties of different modalities (tactile and acoustic). For this, we designed a bimodal detection task where the senses of touch and hearing compete from trial to trial. Two Rhesus monkeys performed this novel task, while neural activity was recorded in areas 3b and 1 of the primary somatosensory cortex (S1). We analyzed neurons’ coding properties and variability, organizing them by their receptive field’s position relative to the stimulation zone. Our results indicate that neurons of areas 3b and 1 are unimodal, encoding only the tactile modality, both in the firing rate and variability, but not to the acoustic one. Moreover, we found that neurons of both subareas encode the tactile information differently, revealing a hidden processingbased hierarchy. Finally, using a powerful non-linear dimensionality reduction algorithm, we show that the activity from areas 3b and 1 can be separated, establishing a clear division in the functionality of these two subareas of S1.

SIGNIFICANCE STATEMENT

Our brain integrates information from all our senses to perceive the external world. But where and how in the brain this integration occurs? Here we ask if the primary somatosensory cortex (S1) encodes information from more than one sensory modality. We recorded the activity of single neurons from areas 3b and S1, while trained monkeys performed a bimodal detection task, where tactile and acoustic stimuli compete. The analysis showed that neurons from areas 3b and 1 responded only to the tactile modality both in their rate and variability. However, our results support that these two areas are different enough as to be considered functionally distinct entities.
Maximum tree lifespans derived from public-domain dendrochronological data
Authors: Biondi Franco , Meko David , Piovesan Gianluca
Published: August 2022

The public-domain International Tree-Ring Data Bank (ITRDB) is an under-utilized dataset to improve existing estimates of global tree longevity. Since dendrochronologists have usually targeted the oldest trees in a stand, this public-domain resource is bound to offer better estimates of maximum tree age than those available from randomized plots or grid-based forest inventories. We used the longest continuous ring-width series of existing ITRDB collections as an index of maximum tree age for that species and site. Using a total of 3679 collections, we obtained longevity estimates for 236 unique tree species, 156 conifers and 80 angiosperms, distributed all over the world. More than half of the species (167) were represented by no more than 10 collections, and a similar number of species (144) reached longevity greater than 300 years. Maximum tree ages exceeded 1000 years for several species (22), all of them conifers, while angiosperm longevity peaked around 500 years. As new collections are constantly being added to the ITRDB, estimates of tree longevity may change slightly, mainly by adding new species to the database. Given the current emphasis on identifying human-induced impacts on global systems, detailed analyses of ITRDB holdings provide one of the most reliable sources of information for tree longevity as an ecological trait.

Key Message

Baseline information on tree longevity was derived from the most extensive dendrochronological database currently available. The resulting summary provides a reference point, to be used for modeling and research purposes.
RaPiD-chamber: Easy to self-assemble live-imaging chamber with adjustable LEDs allows to track small differences in dynamic plant movement adaptation on tissue level
Authors: Kashkan Ivan , García-González Judith , Lacek Jozef , Müller Karel , Růžička Kamil , Retzer Katarzyna , Weckwerth Wolfram
Published: August 2022

Plants rely on fine-tuning organ movement to ensure their survival and productivity. Even subtle loss of directional growth orchestration can result in a huge impact when the plant is impaired to adapt to an ever-changing environment, where it is exposed to manifold exogenous stimuli simultaneously. We present a newly designed chamber to obtain live images to track organ growth and movement differences, called RaspberyPi Dark Chambers (RaPiD-chamber). The RaPiD-chamber is easy to self-assemble and cost-efficient and allows to monitor the continuous growth of etiolated seedlings, as well as their response to light of different wavelengths and from chosen positions. We tested the advice by comparing hypocotyl elongation rate and response to unilateral white and blue light exposure of Arabidopsis thaliana Col0. Additionally, we compared the elongation rate of etiolated hypocotyls between Col0 and kin10, a mutant lacking the catalytic subunit of the cellular signaling hub SUCROSE NON-FERMENTING RELATED KINASE 1 (SnRK1). kin10 is known for its diminished ability to control hypocotyl elongation. As a case study, we compared the growth dynamics of etiolated Col0 versus kin10. Without further energy source supplementation to the growth medium, the mutant cannot keep up with hypocotyl elongation. Additionally, continuous observation of the dark-grown seedlings allowed us to determine a shift in the dynamics of apical hook angle formation for the mutant.
pYtags enable spatiotemporal measurements of receptor tyrosine kinase signaling in living cells
Authors: Farahani Payam E. , Yang Xiaoyu , Mesev Emily V. , Fomby Kaylan A. , Bashor Caleb J. , Nelson Celeste M. , Toettcher Jared E.
Published: August 2022

Receptor tyrosine kinases (RTKs) are major signaling hubs in metazoans, playing crucial roles in cell proliferation, migration, and differentiation. However, few tools are available to measure the activity of a specific RTK in individual living cells. Here, we present pYtags, a modular approach for monitoring the activity of a user-defined RTK by live-cell microscopy. pYtags consist of an RTK modified with a tyrosine activation motif that, when phosphorylated, recruits a fluorescently labeled tandem SH2 domain with high specificity. We show that pYtags enable the monitoring of a specific RTK on seconds-to-minutes time scales and across subcellular and multicellular length scales. Using a pYtag biosensor for epidermal growth factor receptor (EGFR), we quantitively characterize how signaling dynamics vary with the identity and dose of activating ligand. We show that orthogonal pYtags can be used to monitor the dynamics of EGFR and ErbB2 activity in the same cell, revealing distinct phases of activation for each RTK. The specificity and modularity of pYtags opens the door to robust biosensors of multiple tyrosine kinases and may enable engineering of synthetic receptors with orthogonal response programs.

Highlights

pYtags report on signaling of user-defined RTKs in living cells

EGFR signaling dynamics depend on ligand identity and dimer strength

rthogonal pYtags enable reporter multiplexing

pYtags can report on signaling of endogenously expressed RTKs
Urotensin II-Related Peptides, Urp1 and Urp2, Control Zebrafish Spine Morphology
Authors: Bearce Elizabeth A. , Irons Zoe H. , O’Hara-Smith Johnathan R. , Kuhns Colin J. , Fisher Sophie I. , Crow William E. , Grimes Daniel T.
Published: August 2022

The spine provides structure and support to the body, yet how it develops its characteristic morphology as the organism grows is little understood. This is underscored by the commonality of conditions in which the spine curves abnormally such as scoliosis, kyphosis and lordosis. Understanding the origin of such spinal curves has been challenging in part due to the lack of appropriate animal models. Recently, zebrafish have emerged as promising tools with which to understand the origin of spinal curves. Using zebrafish, we demonstrate that the Urotensin II-related peptides (URPs), Urp1 and Urp2, are essential for maintaining spine morphology. Urp1 and Urp2 are 10-amino acid cyclic peptides expressed by neurons lining the central canal of the spinal cord. Upon combined genetic loss of Urp1 and Urp2, adolescent-onset planar curves manifested in the caudal region of the spine, akin to a lordosis-like condition. Highly similar curves were caused by mutation of Uts2r3, an URP receptor. Quantitative comparisons revealed that Urotensin-associated curves were distinct from other zebrafish spinal curve mutants that more closely reflected idiopathic scoliosis or kyphosis. Last, we found that the Reissner fiber, a proteinaceous thread that sits in the central canal and has been implicated in the control of spine morphology, breaks down prior to curve formation in an idiopathic scoliosis model but was unperturbed by loss of Uts2r3. This suggests a Reissner fiber-independent mechanism of curvature in Urotensin-deficient mutants. Overall, our results show that Urp1 and Urp2 control zebrafish spine morphology and establish new animal models of lordosis-like curves.
DNARecords: An extensible sparse format for petabyte scale genomics analysis
Authors: Manas Andres , Seninge Lucas , Dixit Atray
Published: August 2022

Recent growth in population scale sequencing initiatives involve both cohort scale and proportion of genome surveyed, with a transition from genotyping arrays to broader genome sequencing approaches. The resulting datasets can be challenging to analyze. Here we introduce DNARecords a novel sparse-compatible format for large scale genetic data. The structure enables integration of complex data types such as medical images and drug structures towards the development of machine learning methods to predict disease risk and drug response. We demonstrate its speed and memory advantages for various genetics analyses. These performance advantages will become more pronounced as it becomes feasible to analyze variants of lower population allele frequencies. Finally, we provide an open-source software plugin, built on top of Hail, to allow researchers to write and read such records as well as a set of examples for how to use them.
Tissue-Like 3D Standard and Protocols for Microscope Quality Management
Authors: Abrams Benjamin , Pengo Thomas , Wee Tse-Luen , Deagle Rebecca C. , Vuillemin Nelly , Callahan Linda M. , Smith Megan A. , Kubow Kristopher E. , Girard Anne-Marie , Rappoport Joshua Z. , Bayles Carol J. , Cameron Lisa A. , Cole Richard , Brown Claire M.
Published: August 2022

This article outlines a global study conducted by the Association of Biomedical Resource Facilities (ABRF) Light Microscopy Research Group (LMRG). The results present a novel 3D tissue-like biologically relevant standard sample that is affordable and straightforward to prepare. Detailed sample preparation and instrument specific image acquisition protocols and image analysis methods are presented and made available to the community. The standard consists of sub-resolution and large well characterized relative intensity fluorescence microspheres embedded in a 120 µm thick 3D gel with a refractive index of 1.365. The standard allows the evaluation of several properties as a function of depth. These include: 1) microscope resolution with automated analysis of the point spread function (PSF), 2) automated signal-to-noise- ratio analysis, 3) calibration and correction of fluorescence intensity loss, and 4) quantitative relative intensity. Results demonstrate expected refractive index mismatch dependent losses in intensity and resolution with depth but the relative intensities of different objects at similar depths were maintained. This is a robust standard showing reproducible results across laboratories, microscope manufacturers and objective lens types (e.g. magnification, immersion medium). Thus, these tools will be valuable for the global community to benchmark fluorescence microscopes and will contribute to improved rigor and reproducibility.
The Interactions of Potassium Hydroxide in the Vicinity of Connective Disulfide Bonds of the Fab Regions of Some Human Immunoglubulins: Preliminary Computational Implications for Affinity on Cys-Cys Disulfide Bridges
Authors: Zumrutdal Emin
Published: August 2022

The average human lifespan continues to increase with the increase in data flow and the advancement of related technological developments. However, this development brings with it many diseases, including immunological problems. Immunoglobulin varieties found in different organisms in the last 3-4 decades continue to be hope for many diseases.

Interest has focused on the lesser weight but more mobile immunoglobulins found in camelids. Later, different types of these antibodies were tried to be made with biotechnological engineering and their effectiveness continues to be investigated. Disulfide bridges located on the immunoglobulin are one of the key points for the structure and function of the immunoglobulin. The interest of potassium hydroxide in disulfide bridges may enable us to damage or break these bonds. For this purpose, in this study, the relationship between disulfide bridges between light and heavy chains and potassium hydroxide was investigated. It was observed that the affinity of potassium hydroxide to disulfide bridges occurred exergonically. In the light of this information, it can be thought that lighter, more functional immunoglobulin fragments and nanobodies can be formed with potassium hydroxide compared to conventional immunoglobulin.
ENVIROME-WIDE ASSOCIATIONS ENHANCE MULTI-YEAR GENOME-BASED PREDICTION OF HISTORICAL WHEAT BREEDING DATA
Authors: Costa-Neto Germano , Crespo-Herrera Leonardo , Fradgley Nick , Gardner Keith , Bentley Alison R. , Dreisigacker Susanne , Fritsche-Neto Roberto , Montesinos-López Osval A. , Crossa Jose
Published: August 2022

Linking high-throughput environmental data (enviromics) into genomic prediction (GP) is a cost-effective strategy for increasing selection intensity under genotype-by-environment interactions (G×E). This study developed a data-driven approach based on Environment-Phenotype Associations (EPA) aimed at recycling important G×E information from historical breeding data. EPA was developed in two applications: (1) scanning a secondary source of genetic variation, weighted from the shared reaction-norms of past-evaluated genotypes; (2) pinpointing weights of the similarity among trial-sites (locations), given the historical impact of each envirotyping data variable for a given site. Then, the EPA outcomes were integrated into multi-environment GP models through a new single-step GBLUP. The wheat trial data used included 36 locations, 8 years and 3 target populations of environments (TPE) in India. Four prediction scenarios and 6 kernel-models within/across TPEs were tested. Our results suggest that the conventional GBLUP, without enviromic data or when omitting EPA, is inefficient in predicting the performance of wheat lines in future years. However, when EPA was introduced as an intermediary learning step to reduce the dimensionality of the G×E kernels while connecting phenotypic and environmental-wide variation, a significant enhancement of G×E prediction accuracy was evident. EPA revealed that the effect of seasonality makes strategies such as “covariable selection” unfeasible because G×E is year-germplasm specific. We propose that the EPA effectively serves as a “reinforcement learner” algorithm capable of uncovering the effect of seasonality over the reaction-norms, with the benefits of better forecasting the similarities between past and future trialing sites. EPA combines the benefits of dimensionality reduction while reducing the uncertainty of genotype-by-year predictions and increasing the resolution of GP for the genotype-specific level.
Amodal population clock in the primate medial premotor system for rhythmic tapping
Authors: Betancourt Abraham , Pérez Oswaldo , Gámez Jorge , Mendoza Germán , Merchant Hugo
Published: August 2022

The neural substrate for beat extraction and response entrainment to auditory and visual rhythms is still unknown. Here we analyzed the population activity of hundreds of medial premotor neurons of monkeys performing an isochronous tapping guided by brief flashing stimuli or auditory tones. The animals showed a strong bias towards visual than auditory metronomes, with rhythmic tapping that was more precise and accurate on the former. The population dynamics shared the following properties across modalities: the circular dynamics of the neural trajectories formed a regenerating loop for every produced interval; the trajectories converged in similar state space at tapping times resetting the clock; the tempo of the synchronized tapping was encoded in the trajectories by a combination of amplitude modulation and temporal scaling. In addition, the modality induced a displacement in the neural trajectories in auditory and visual subspaces without greatly altering time keeping mechanism. These results suggest that the interaction between the MPC amodal internal representation of pulse and a modality specific external input generates a neural rhythmic clock whose dynamics governs rhythmic tapping execution across senses.
Plasticity and lineage commitment of individual Th1 cells are determined by stable T-bet expression quantities
Authors: Hegazy Ahmed N. , Peine Caroline , Niesen Dominik , Panse Isabel , Vainshtein Yevhen , Kommer Christoph , Zhang Qin , Brunner Tobias M. , Peine Michael , Fröhlich Anja , Ishaque Naveed , Marek Roman M. , Zhu Jinfang , Höfer Thomas , Löhning Max
Published: August 2022

T helper 1 (Th1) cell identity is defined by the expression of the lineage-defining transcription factor T-bet. Here, we examine the influence of T-bet expression heterogeneity on subset plasticity by leveraging cell sorting of distinctin vivo-differentiated Th1 cells based on their quantitative expression of T-bet and interferon-γ. Heterogeneous T-bet expression states were regulated by virus-induced type-I interferons and were stably maintained even after secondary viral infection. Exposed to Th2-polarizing conditions, the sorted subpopulations exhibited graded levels of plasticity: T-bet quantities were inversely correlated with the ability to express the Th2 lineage-specifying transcription factor GATA-3 and Th2 cytokines. Reprogramed Th1 cells acquired graded, but stable mixed Th1+2 phenotypes with a hybrid epigenetic landscape. Continuous presence of T-bet in differentiated Th1 cells was essential to ensure Th1 cell stability. Thus, innate cytokine signals regulate Th1 cell plasticity via an individual cell-intrinsic rheostat to enable T cell subset adaptation to subsequent challenges.

HIGHLIGHTS

Type-I interferons triggered by infection determine T-bet expression states in Th1 cells

T-bet and IFN-γ expression states indicate the plasticity of individual Th1 cells

Individual T-bet expression states and plasticity persist after secondary infection

Reprogramming yields stable Th1+2 phenotypes and a mixed epigenetic landscape
Evasion of Neutralizing Antibody Response by the SARS-CoV-2 BA.2.75 Variant
Authors: Qu Panke , Evans John P. , Zheng Yi-Min , Carlin Claire , Saif Linda J. , Oltz Eugene M. , Xu Kai , Gumina Richard J. , Liu Shan-Lu
Published: August 2022

The newly emerged BA.2.75 SARS-CoV-2 variant exhibits an alarming 9 additional mutations in its spike (S) protein compared to the ancestral BA.2 variant. Here we examine the neutralizing antibody escape of BA.2.75 in mRNA-vaccinated and BA.1-infected individuals, as well as the molecular basis underlying functional changes in the S protein. Notably, BA.2.75 exhibits enhanced neutralization resistance over BA.2, but less than the BA.4/5 variant. The G446S and N460K mutations of BA.2.75 are primarily responsible for its enhanced resistance to neutralizing antibodies. The R493Q mutation, a reversion to the prototype sequence, reduces BA.2.75 neutralization resistance. The mutational impact is consistent with their locations in common neutralizing antibody epitopes. Further, the BA.2.75 variant shows enhanced cell-cell fusion over BA.2, driven largely by the N460K mutation, which enhances S processing. Structural modeling revealed a new receptor contact introduced by N460K, supporting a mechanism of potentiated receptor utilization and syncytia formation.
Unconventional Initiation of PINK1/Parkin Mitophagy by Optineurin
Authors: Nguyen Thanh Ngoc , Sawa-Makarska Justyna , Khuu Grace , Lam Wai Kit , Adriaenssens Elias , Fracchiolla Dorotea , Shoebridge Stephen , Padman Benjamin Scott , Skulsuppaisarn Marvin , Lindblom Runa S.J. , Martens Sascha , Lazarou Michael
Published: August 2022

Cargo sequestration is a fundamental step of selective autophagy in which cells generate a double membrane structure termed an autophagosome on the surface of cargoes. NDP52, TAX1BP1 and p62 bind FIP200 which recruits the ULK1/2 complex to initiate autophagosome formation on cargoes. How OPTN initiates autophagosome formation during selective autophagy remains unknown despite its importance in neurodegeneration. Here, we uncover an unconventional path of PINK1/Parkin mitophagy initiation by OPTN that does not begin with FIP200 binding nor require the ULK1/2 kinases. Using gene-edited cell lines andin vitroreconstitutions, we show that OPTN utilizes the kinase TBK1 which binds directly to the class III phosphatidylinositol 3-kinase complex I to initiate mitophagy. During NDP52 mitophagy initiation, TBK1 is functionally redundant with ULK1/2, classifying TBK1’s role as a selective autophagy initiating kinase. Overall, this work reveals that OPTN mitophagy initiation is mechanistically distinct and highlights the mechanistic plasticity of selective autophagy pathways.
Multiomics and quantitative modelling disentangle diet, host, and microbiota contributions to the host metabolome
Authors: Zimmermann-Kogadeeva Maria , Bencivenga-Barry Natasha A. , Zimmermann Michael , Bork Peer , Goodman Andrew L.
Published: August 2022

Dietary nutrients, host metabolism, and gut microbiota activity each influence the host’s metabolic phenotype; however, the interplay between these factors remains poorly understood. We employed tissue-resolved metabolomics in gnotobiotic mice carrying a synthetic human gut microbiota and germfree mice in two dietary conditions to develop an intestinal flux model that quantifies diet, host, and bacterial contributions to the levels of 2,700 intestinal metabolites. While diet was the main factor affecting metabolite profiles, we identified 1,117 potential microbial substrates and products in the gut. By integrating metagenomics and metatranscriptomics data into genome-scale enzymatic networks, we linked 202 potential substrate-product pairs by a single enzymatic reaction. We further identified bacterial species and enzymes that can explain the differential abundance of 13% of the identified microbial products between the mouse groups. This quantitative modelling approach paves the way for controlling an individual’s metabolic phenotype by modulating their gut microbiome composition and diet.
Target sequence capture data shed light on the deeper evolutionary relationship on the subgenus Chamaecerasus of Lonicera (Caprifoliaceae)
Authors: Sun Qing-Hui , Morales-Briones Diego F. , Wang Hong-Xin , Landis Jacob B. , Wen Jun , Wang Hua-Feng
Published: August 2022

The genus Lonicera L. is widely distributed and is well-known for its high species richness and morphological diversity. Previous studies have suggested that many sections of Lonicera are not monophyletic and phylogenetic relationships within the genus are still poorly known. In this study, we sampled 37 accessions of Lonicera, covering four sections of subgenus Chamaecerasus plus six outgroup taxa to recover the main clades of Lonicera based on sequences of nuclear loci generated by target enrichment and cpDNA from genome skimming. We found extensive cytonuclear discordance across the subgenus. Both nuclear and plastid phylogenetic analyses supported subgenus Chamaecerasus sister to subgenus Lonicera. Within subgenus Chamaecerasus, sections Isika and Niatoon were polyphyletic. Based on the nuclear and chloroplast phylogenies we propose to merge Lonicera korolkowii into section Coeloxylosteum and Lonicera caerulea into section Nintooa. In addition, Lonicera is estimated to have originated in the late Miocene (19.84 Ma). The stem age of section Nintooa was estimated to be 17.97 Ma (95% HPD: 13.31- 22.89). The stem age of subgenus Lonicera was estimated to be 16.35 Ma (95% HPD: 9.33- 45.15). Ancestral area reconstruction analyses indicate that Lonicera originated in the Qinghai Tibet Plateau (QTP) and Asia, with subsequent dispersal into other areas. The aridification of the Asian interior possibly promoted the rapid radiation of Lonicera within this region, and the uplift of the QTP appears to have triggered the dispersal and recent rapid diversification of the genus in the QTP and adjacent regions. Overall, this study provides new insights into the taxonomically complex lineages of Lonicera at the section level and the process of speciation.
Pervasive SUMOylation of heterochromatin and piRNA pathway proteins
Authors: Ninova Maria , Holmes Hannah , Lomenick Brett , Fejes-Tóth Katalin , Aravin Alexei A.
Published: August 2022

Genome regulation involves complex and highly regulated protein interactions that are often mediated through post-translational modifications (PTMs). SUMOylation – the covalent attachment of thesmallubiquitin-likemodifier (SUMO) – is a conserved PTM in eukaryotes that has been implicated in a number of essential processes such as nuclear import, DNA damage repair, transcriptional control, and chromatin organization. InDrosophila, SUMO is essential for viability and its depletion from the female germline causes infertility associated with global loss of heterochromatin, and illicit upregulation of transposons and lineage-inappropriate genes. However, the specific targets of SUMO and its mechanistic role in different cellular pathways are still poorly understood. Here, we developed a proteomics-based strategy to characterize the SUMOylated proteome inDrosophilathat allowed us to identify ~1500 SUMO sites in 843 proteins in the fly ovary. A high-confidence set of SUMOylated proteins is highly enriched in factors involved in heterochromatin regulation and several different aspects of the piRNA pathway that represses transposons, including piRNA biogenesis and function. Furthermore, we show that SUMOylation of several piRNA pathway proteins occurs in a Piwi-dependent manner, indicating a functional implication of this modification in the cellular response to transposon activity. Together, these data highlight the impact of SUMOylation on epigenetic regulation and reveal an unexpectedly broad role of the SUMO pathway in the cellular defense against genomic parasites. Finally, this work provides a valuable resource and a system that can be adapted to the study of SUMOylation in otherDrosophilatissues.
Evaluating methods for estimating the proportion of adaptive amino acid substitutions
Authors: Al-Saffar Samer I. , Hahn Matthew W.
Published: August 2022

A long-standing debate in molecular evolution concerns the role of adaptation in shaping divergence between species. A number of approaches have been developed to estimate the proportion of amino acid substitutions between species (α) that are driven by adaptive natural selection. These methods vary in the type of data they use and in the modeling strategies they employ in their inference. In this study, we evaluate the accuracy of nine different methods for estimating α, using data simulated in the presence of linked selection. We find that methods that model the distribution of fitness effect (DFE) of both deleterious (as a gamma distribution) and beneficial mutations (as a gamma or exponential distribution) are the most accurate. We applied these methods to whole-genome data, finding that the most accurate methods gave average values of α=0.25 in Arabidopsis thaliana, 0.5 in Drosophila melanogaster, and 0.1 in Homo sapiens. We also applied these methods to analyze subsets of tissue-specific genes in A. thaliana that are believed to be under different selective pressures and on genes found on the X vs. autosomes in D. melanogaster. We find estimates of α to be higher in the seeds than in other specialized organs, supporting inferences of conflict-driven adaptive evolution in genes expressed in the seed; we also find α to be higher on the X chromosome, supporting previous inferences of faster-X evolution. Overall, our results suggest that there are multiple methods that provide accurate estimates of α, providing a guide for future estimates of adaptive evolution.
Limosilactobacillus fermentum-fermented ginseng improved antibiotic-induced diarrhoea and the gut microbiota profiles of rats
Authors: Qu Qingsong , Zhao Chongyan , Yang Cuiting , Zhou Qing , Liu Xing , Yang Pengshuo , Yang Fang , Shi Xinyuan
Published: August 2022

Aims

This study investigated the efficacy of Limosilactobacillus fermentum-fermented ginseng for improving colitis and the gut microbiota profiles in rats and explored the benefits of the L. fermentum fermentation process to ginseng.

Methods and results

Ginseng polysaccharide and ginsenoside from fermented ginseng were analysed by UV and HPLC. Antibiotic-fed rats were treated with fermented ginseng and a L. fermentum–ginseng mixture. Histopathology- and immune-related factors (TNF-α, IL-1β, IL-6 and IL-10) of the colon were assayed by using pathological sections and ELISA. After treatment, fermented ginseng relieved the symptoms of antibiotic-induced diarrhoea and colon inflammation, and the expression of colon immune factors returned to normal. The gut microbial communities were identified by 16S rRNA gene sequencing. The results showed that the alterations in the gut microbiota returned to normal. In addition, the gut microbiota changes were correlated with immune factor expression after treatment. The fermented ginseng had better biological functions than a L. fermentum–ginseng mixture.

Conclusions

Fermented ginseng can relieve diarrhoea and colon inflammation and restore the gut microbiota to its original state. The process of L. fermentum fermentation can expand the therapeutic use of ginseng.

Significance and impact of the study

This research suggested the potential function of fermented ginseng to relieve diarrhoea and recover the gut microbiota to a normal level and explored the benefits of the Limosilactobacillus fermentum fermentation process to ginseng.
Detection of the HLA‐A*02:759 allele, a variant of A*02:06:01:01, in a Taiwanese individual
Authors: Yang Kuo‐Liang , Lin Py‐Yu
Published: August 2022

A nucleotide mutation in exon 1 of HLA‐A*02:06:01:01 results in the novel allele, HLA‐A*02:759.
In Memoriam: Professor Richard B. Stein (1940–2020) harnessing insights from the neurophysiology of motor control—from bench to bedside
Authors: Gordon Tessa , Everaert Dirk G. , Chan K. Ming
Published: August 2022

The role of afferent feedback and central motor drive in muscle activation has a profound impact on our understanding of movement control in health and disease. Dr. Richard B. Stein was a pioneer who made major contributions to the field. In addition to fundamental discoveries using animal models, he translated this to the clinic to benefit patients with spinal cord and other neurological injuries. Along the way, he inspired a generation of scientists around the world.
Why be ethical
Authors: Almualla Suad
Published: August 2022

Some might ask: why should I be ethical? Life would be much easier if I cheated my way out in life! There are a number of reasons for why people want to be ethical. For one, being ethical is in our selfinterest. We can protect our community and eventually ourselves if we act responsibly at work preventing unethical practices and fraud and being the best at what we are doing. Life will not look so rosy if we cheated, embezzled, or murdered people. People could hate us, boycott us, call the cops, or attempt to murder us. We could lose reputation or go bankrupt.
GoodIT summary
Authors: Goldweber Mikey
Published: August 2022

In 2015, a trio of European academic computer scientists, Ombretta Gaggi, Pietro Manzoni, and Claudio Palazzi, launched a new conference: GoodTechs: The EAI International Conference on Smart Objects and Technologies for Social Good. GoodTechs grew over the next six years. For 2021 the original trio split with EAI and formed GoodIT as an ACM/SIGCAS sponsored conference; The ACM Conference on Information Technology for Social Good (GoodIT).
The Role of TAMs in Tumor Microenvironment and New Research Progress
Authors: Feng Yawei , Ye Zhiqiang , Song Furong , He Yufeng , Liu Jun
Published: August 2022

Tumor-associated macrophages (TAMs) are an important part of tumor microenvironment (TME) and play a key role in TME, participating in the process of tumor occurrence, growth, invasion, and metastasis. Among them, metastasis to tumor tissue is the key step of malignant development of tumor. In this paper, the latest progress in the role of TAMs in the formation of tumor microenvironment is summarized. It is particularly noteworthy that cell and animal experiments show that TAMs can provide a favorable microenvironment for the occurrence and development of tumors. At the same time, clinical pathological experiments show that the accumulation of TAMs in tumor is related to poor clinical efficacy. Finally, this paper discusses the feasibility of TAMs-targeted therapy as a new indirect cancer therapy. This paper provides a theoretical basis for finding a potentially effective macrophage-targeted tumor therapy.
Esse poema também é um grande sonho
Authors: Vieira Leonardo Martins
Published: August 2022

Poema de Leonardo Martins Vieira Vieira
Young People’s Embodied Hope in Pandemic Threats
Authors: Christian Ivan , Susanta Yohanes Krismantyo
Published: August 2022

Young people today are both likely to bear the brunt of the long-term problems caused by the covid-19 pandemic and face other kinds of outbreaks or pandemics in the future. In that kind of unprecedented situation, the world offers us hope to recover from today’s pandemic and to prevent other outbreaks or pandemics in the future. This study will focus on a theological reflection on hope concerning pandemic threats offered in popular culture. Specifically, using the revised correlational method, this study will explore how the theological reflection on the concept of hope in Netflix’s Pandemic docuseries could help young people to live with an embodied hope in a pandemic threat. This theological reflection will offer embodied hope as a theological perspective for young people to embody their limitations as embodied beings while enacting their eschatological hope in pandemic threats.
One Versus Two Stents Strategies for Unprotected Left Main Intervention: Gulf Left Main Registry
Authors: Alasmari Abdulaziz , Iskandar Mina , Daoulah Amin , Hersi Ahmad S. , Alshehri Mohammed , Aljohar Alwaleed , Al Garni Turki , Abuelatta Reda , Yousif Nooraldaem , Almahmeed Wael , Kazim Hameedullah M. , Refaat Wael , Selim Ehab , Alzahrani Badr , Alqahtani Abdulrahman H. , Ajaz Ghani Mohamed , Amin Haitham , Hashmani Shahrukh , El-Sayed Osama , Jamjoom Ahmed , Hurley William T. , Dahdouh Ziad , Aithal Jairam , Ahmad Osama , Ramadan Mohamed , Ibrahim Ahmed M. , Elganady Abdelmaksoud , Qutub Mohammed A. , Alama Mohamed N. , Abohasan Abdulwali , Hassan Taher , Balghith Mohammed , Altnji Issam , Hussien Adnan Fathey , Abdulhabeeb Ibrahim A. M. , Qenawi Wael , Shawky Ahmed , Ghonim Ahmed A. , Elmahrouk Ahmed , Hiremath Niranjan , Jameel Naser Maryam , Shawky Abeer M. , Lotfi Amir
Published: August 2022

The optimal stenting strategy for unprotected left main coronary artery (ULMCA) disease remains debated. This retrospective observational study (Gulf Left Main Registry) analyzed the outcomes of 1 vs 2 stents in patients with unprotected left main percutaneous coronary intervention (PCI). Overall, 1222 patients were evaluated; 173 had 1 stent and 1049 had 2 stents. The 2-stent group was older with more comorbidities, higher mean SYNTAX scores, and more distal bifurcation lesions. In the 1-stent group, in-hospital events were significant for major bleeding, and better mean creatinine clearance. At median follow-up of 20 months, the 1-stent group was more likely to have target lesion revascularization (TLR). Total mortality was numerically lower in the 1-stent group (.00% vs 2.10%); however, this was not statistically significant ( P=.068). Our analysis demonstrates the benefits of a 2-stent approach for ULMCA patients with high SYNTAX scores and lesions in both major side branches, while the potential benefit of a 1-stent approach for less complex ULMCA was also observed. Further studies with longer follow-up are needed to definitively demonstrate the optimal approach.
Exploring the outcomes of enterprise and entrepreneurship education in UK HEIs: An Excellence Framework perspective
Authors: Bozward David , Rogers-Draycott Matthew , Smith Kelly , Mave Mokuba , Curtis Vic , Aluthgama-Baduge Chinthaka , Moon Rob , Adams Nigel
Published: August 2022

The purpose of this paper is to investigate data relating to the outcomes of enterprise and entrepreneurship education (EEE) activity in UK higher education institutions (HEIs). This is achieved via the use of data obtained from the Research Excellence Framework (REF), the Teaching Excellence and Student Outcomes Framework (TEF), the Knowledge Excellence Framework (KEF) and the Higher Education Business and Community Interaction (HE-BCI) survey. Overall, the analysis suggests, powerfully, that EEE impacts research, teaching and knowledge exchange in a variety of ways. Firstly, it shows that EEE, in terms of the REF, may be up to 46 times more impactful than other management disciplines. Secondly, with regard to TEF submissions, it highlights a positive relationship between the use of the EEE terms and the award level achieved. Finally, research also demonstrates a link between membership of certain HEI mission groups and improved KEF metrics when compared to the sector averages. There is a clear need to research how to develop successful EEE interventions and demonstrate their impact on the graduate, the university ecosystem and the wider economy. These data sources and methodology have not previously been used to develop a narrative for EEE across a university sector in the UK.
Power-Sharing, Presidential Style: Issue Salience and Portfolio Allocation in Multiparty Presidential Systems
Authors: Batista Mariana
Published: August 2022

Minority presidents form coalitions to secure legislative support. However, such support comes at the policy cost of delegating power to coalition partners. Given this dilemma, how do presidents decide on portfolio allocation? The argument is that presidents consider ministries' policy relevance and the characteristics of coalition parties when distributing positions. The president will allocate the most important ministries to aligned ministers (seeking policy control) and to the larger coalition parties (seeking legislative support), distributing the least policy-relevant ministries to clientelist parties. The article presents an original measure for policy salience based on topic modeling of presidential addresses and conditional logit models to test the hypotheses. The analysis consists of a comparative study of Brazil, Chile, and Colombia over 24 years. Results indicate that presidents use salience to sort ministries and decide portfolio allocation. This evidence for the president-specific salience argument shows the relevance of considering the qualitative aspects of portfolio allocation in multiparty presidential systems and how presidents share power with coalition partners without losing control over governmental decisions.
What can We Learn From High-Performing Screening Programs to Increase Bowel Cancer Screening Participation in Australia?
Authors: Flander Louisa , Dekker Evelien , Andersen Berit , Larsen Mette Bach , Steele Robert J , Malila Nea , Sarkeala Tytti , van der Vlugt Manon , de Klerk Clasine , Knottnerus Bart , Bertels Lucinda , Woudstra Anke , Spaander Manon C.W. , Fransen Mirjam , Heinavaara Sirpa , Dillon Mary , Ait Ouakrim Driss , Jenkins Mark
Published: August 2022

Background

Colorectal cancer (CRC) is the second most diagnosed cancer in men and women and second most common cause of cancer death in Australia; Australia’s CRC incidence and mortality are among the world’s highest. The Australian National Bowel Cancer Screening Program began in 2006; however, only 33% of those approached for the first time by the Program between 2018 and 2019 returned the kit. Of the 5.7 million kits sent during this period, only 44% were returned. Our aim was to identify practices and features of national bowel cancer screening programs in countries with similar programs but higher screening participation, to identify potential interventions for optimising Australian CRC screening participation.

Methods

We searched published and grey literature for CRC screening programs reporting at least 50% screening participation using postal invitation and free return of iFOBT home kits. Interviews were conducted with cancer registry staff and academic researchers, focused on participant and practitioner engagement in screening.

Results

National programs in Netherlands, Scotland, Denmark, and Finland reported over 50% screening participation rates for all invitation rounds. Shared characteristics include small populations within small geographic areas relative to Australia; relatively high literacy; a one-sample iFOBT kit; national registration systems for population cancer screening research; and screening program research including randomised trials of program features.

Conclusions

Apart from the one-sample kit, we identified no single solution to persistent Australian low uptake of screening. Research including randomised trials within the program promises to increase participation.

Impact

This screening program comparison suggests that within-program intervention trials will lead to increased Australian screening participation.
Open Proximal Endarterectomy with Retrograde Access and Stenting: A Novel Technique for Lower Extremity Revascularization
Authors: Blitzer David N. , Rolle Nicholas P. , Abdou Hossam , Berg Lars , Nagarsheth Khanjan H.
Published: August 2022

Background:

Treatment of chronic limb threatening ischemia (CLTI) poses a significant clinical challenge despite recent medical advancements. Chronic total occlusion (CTO) lesions make endovascular approaches to CLTI particularly challenging. Open proximal exposure with retrograde access and stenting (OPERAS) aims to solve this challenge through retrograde subintimal crossing of a CTO with direct visualization of proximal re-entry into the true lumen. We describe this novel technique and present its efficacy in eight patients.

Methods:

We conducted a retrospective case series at a single tertiary academic center. Data for patients who received OPERAS intervention included demographics, peri-operative details, and follow-up information. Statistical analysis was performed on length of stay, major post-operative complications, further intervention, clinical progression at 1 year, and amputation-free survival at 1 year. Immediate technical failure (ITF) and limb-based patency (LBP) at 1 year were calculated.

Results:

Nine limbs underwent OPERAS between January 2019 and March 2020. Inflow was achieved with common femoral artery endarterectomy. All limbs underwent balloon angioplasty and stenting of the SFA, and seven underwent the same procedure in the popliteal artery. ITF was 0% for all nine cases. There were no major post-operative complications, and ankle-brachial index significantly improved pre-and post-operatively ( P < .001). Eight limbs (88.9%) sustained amputation-free survival at 1 year, and overall LBP was 67% at 1 year.

Conclusion:

Our study presents a hybrid revascularization option to address severe, anatomically complex limbs (GLASS III) that lack a single autogenous conduit for open surgical revascularization. OPERAS addresses a main point of technical failure of subintimal techniques by directly visualizing the wire in the true lumen. Our data suggest that OPERAS can be effective to: (1) improve technical success of luminal re-entry following a subintimal approach; (2) address inflow concurrently with severe femoropopliteal disease; and (3) can be utilized when distal tissue loss is involved.
Test of a Social Cognitive Model of Restorative Well-Being: Application to International Students
Authors: Ezeofor Ijeoma , Lent Robert W. , Moturu Bhanu Priya
Published: August 2022

The social cognitive model of restorative well-being (Lent, 2004) focuses on the means by which people help to stabilize their emotional functioning after exposure to challenging life conditions. We extended this model to the study of how international students navigate psychological adjustment to life in the United States. In this application, we focused on the interplay of cognitive, behavioral, social, and trait mechanisms that may help to mitigate distress and promote well-being in the context of change and transition. Participants were 233 international students at U.S. colleges and universities who completed measures of acculturative stress, life satisfaction, social support, self-efficacy in coping with life changes, general self-efficacy, and acculturation- and enculturation-based coping behaviors. Findings indicated that the model provided good fit to the data. Coping efficacy was strongly predictive of lower levels of acculturative stress, which in turn predicted life satisfaction together with general self-efficacy. We consider implications of the findings for future research as well as for interventions designed to prevent psychological distress and to promote effective coping among international students and in a broad range of other stress and coping contexts, such as life role transitions.
High-Efficient Spin Injection in GaN at Room Temperature Through A Van der Waals Tunnelling Barrier
Authors: Lin Di , Kang Wenyu , Wu Qipeng , Song Anke , Wu Xuefeng , Liu Guozhen , Wu Jianfeng , Wu Yaping , Li Xu , Wu Zhiming , Cai Duanjun , Yin Jun , Kang Junyong
Published: August 2022

Achieving high-efficient spin injection in semiconductors is critical for developing spintronic devices. Although a tunnel spin injector is typically used, the construction of a high-quality tunnel barrier remains a significant challenge due to the large lattice mismatch between oxides and semiconductors. In this work, van der Waals h-BN films with the atomically flat interface were engaged as the tunnel barrier to achieve high spin polarization in GaN, and the spin injection and transport in GaN were investigated systematically. Based on the Hanle precession and magnetic resistance measurements, CoFeB was determined as an optimal spin polarizer, bilayer h-BN tunnelling barrier was proven to yield a much higher spin polarization than the case of monolayer, and appropriate carrier concentration as well as higher crystal equality of n-GaN could effectively reduce the defect-induced spin scattering to improve the spin transport. The systematic understanding and the high efficiency of spin injection in this work may pave the way to the development of physical connotations and the applications of semiconductor spintronics.