bluuebunny/crossref_metadata_2025 huggingface dataset:
Visual function impairment in patients suffering from visually induced motion sickness. A preliminary observational longitudinal study
Authors: Gabriele Leonardo , De Angelis Sara , Roncagli Vittorio , Tramontano Marco , Manzari Leonardo , Gabriele Domenico
Published: January 2023

Objective

Visually induced Motion Sickness (VIMS) is a side effect induced by the physical motion of the person or visual motion that adversely affects otherwise individuals and decreases safety in situations that require high levels of concentration. The exact mechanisms behind the emergence of VIMS are still unknown but can be triggered by direct or indirect stimuli due to mismatches in the visual-vestibular autonomic pathways. The aim of this preliminary study was to explore the presence of visual dysfunctions in patients suffering from VIMS and then evaluate the potential role of a customized visual training (VT) on their perceived sickness symptoms.

Methods

A total of 9.675 medical records of patients who referred motion sickness were reviewed; 455 patients with a diagnosis of VIMS were included. A total of 95 patients (86 females and 9 males, mean age of 37,68 ± 9.20 years) met the inclusion criteria and were enrolled in this study. Two evaluation sessions were carried out immediately before (T0) and after 16 weeks (T1) of visual training (VT). The main goal of VT was to facilitate the visual center-periphery integration. VT was performed 1 day/week/16 weeks under therapist supervision in the Optometric centre and 5 days/week/16 weeks at home without supervision.

Results

The within-subjects comparison at times T0–T1 showed significant improvement of the symptoms in all the included patients.

Conclusion

Our results support the hypothesis that patients suffering from VIMS may present also a visual function impairment that can increase the dizziness-related symptoms. Furthermore, visual training can help patients with VIMS and visual dysfunction in reducing capture discomfort, stomach awareness, and nausea.
TIMP-1 is a novel ligand of Amyloid Precursor Protein and triggers a proinflammatory phenotype in human monocytes
Authors: Eckfeld Celina , Schoeps Benjamin , Häußler Daniel , Frädrich Julian , Bayerl Felix , Böttcher Jan Philipp , Knolle Percy , Heisz Simone , Prokopchuk Olga , Hauner Hans , Munkhbaatar Enkhtsetseg , Demir Ihsan Ekin , Hermann Chris D. , Krüger Achim
Published: January 2023

The emerging cytokine tissue inhibitor of metalloproteinases-1 (TIMP-1) correlates with the progression of inflammatory diseases, including cancer. However, the effects of TIMP-1 on immune cell activation and underlying molecular mechanisms are largely unknown. Unbiased ligand-receptor-capture-screening revealed TIMP-1-interaction with Amyloid Precursor Protein (APP) family members, namely APP and Amyloid Precursor-like Protein-2 (APLP2), which was confirmed by pull-down assays and confocal microscopy. We found that TIMP-1 triggered glucose uptake and proinflammatory cytokine expression in human monocytes. In cancer patients, TIMP-1 expression positively correlated with proinflammatory cytokine expression and processes associated with monocyte activation. In pancreatic cancer, TIMP-1 plasma levels correlated with the monocyte activation marker sCD163, and the combined use of both clinically accessible plasma proteins served as a powerful prognostic indicator. Mechanistically, TIMP-1 triggered monocyte activation by its C-terminal domain and via APP as demonstrated by in vitro interference, in silico docking, and the employment of recombinant TIMP-1 variants. Identification of TIMP-1 as a trigger of monocyte activation opens new therapeutic perspectives for inflammatory diseases.
Effects of phonon bandgap on phonon–phonon scattering in ultrahigh thermal conductivity θ-phase TaN
Authors: Wu Chao , Liu Chenhan
Published: January 2023

Phonon bandgap typically has a significant effect on phonon–phonon scattering process. In this work, the effects of mass modified phonon bandgap in θ-phase TaN are systemically investigated by the means of first-principles calculations with linearized Boltzmann transport equation. Through detailed calculations, we find that phonon bandgap has a significant effect on three-phonon process while exhibits a much weaker effect on four-phonon process. The reason for the ultrahigh thermal conductivity of θ-phase TaN is the long lifetime of phonons including both three-phonon and four-phonon processes, which originates from the weak phonon anharmonicity and large phonon bandgap-induced small phonon–phonon scattering phase space. This work advances the understanding of phonon bandgap effects on phonon transport.
Burst Phase Distribution of SGR J1935+2154 Based on Insight-HXMT
Authors: Lu Xue-Feng , Song Li-Ming , Ge Ming-Yu , Tuo You-Li , Zhang Shuang-Nan , Qu Jin-Lu , Cai Ce , Xie Sheng-Lun , Liu Cong-Zhan , Li Cheng-Kui , Fu Yu-Cong , Xu Ying-Chen , Li Tian-Ming
Published: January 2023

On 2020 April 27, the soft gamma-ray repeater SGR J1935+2154 entered its intense outburst episode again. Insight-HXMT carried out about one month observation of the source. A total number of 75 bursts were detected during this activity episode by Insight-HXMT, and persistent emission data were also accumulated. We report on the spin period search result and the phase distribution of burst start times and burst photon arrival times of the Insight-HXMT high energy detectors and Fermi/Gamma-ray Burst Monitor (GBM). We find that the distribution of burst start times is uniform within its spin phase for both Insight-HXMT and Fermi/GBM observations, whereas the phase distribution of burst photons is related to the type of a burst’s energy spectrum. The bursts with the same spectrum have different distribution characteristics in the initial and decay episodes for the activity of magnetar SGR J1935+2154.
Effects of long-term annealing-induced microstructure evolution on mechanical performance and deuterium release behavior of Li4SiO4 pebbles
Authors: Gu S. , Ji B. , Wang C. , Qi Q. , Zhou H.-S. , Zhang Y. , Luo G.-N.
Published: January 2023

Lithium-based ceramic breeder Li4SiO4 will suffer long-term high temperature during operation. That may lead to changes to its microstructure, chemical phase, composition elements, and further impacts its mechanical performance and hydrogen isotope release behavior. In the present work, long-term annealing at 900 °C in He incl. 0.1 vol% H2 flow atmosphere for designated times was conducted. Li4SiO4 pebbles with poor or excellent mechanical performance (abbr. “poor pebbles” and “excellent pebbles”) have porous or dense microstructure, respectively. Coarsening process that grains and pores get larger as a function of annealing time was observed for Li4SiO4 poor pebbles. Li4SiO4 excellent pebbles can maintain its microstructure stability, and only slight grain growth was observed after 1000 h of annealing. Oxygen and lithium element loss was demonstrated over annealing time. Compression tests and Weibull analysis indicate that the distinct degradation of mechanical performance of Li4SiO4 pebbles mainly occur in the initial 100 h of annealing, and then the degradation process slows down. Thermal desorption spectroscopy reveals that 1000 h of annealing caused the disappearance of high temperature release peak (665 °C) and the shift of low temperature release peaks (around 300 °C) to lower temperature. The former is mainly attributed to decomposition of carbon impurities (Li2CO3) and the latter is attributed to carbon impurities and the transition from closed to open pores.
Mapping electric vehicle impacts: greenhouse gas emissions, fuel costs, and energy justice in the United States
Authors: Vega-Perkins Jesse , Newell Joshua P , Keoleian Gregory
Published: January 2023

The transition to electric vehicles (EVs) will impact the climate, the environment, and society in highly significant ways. This study compares EVs to vehicles with internal combustion engines for three major areas: greenhouse gas emissions (GHGs), fuel costs, and transportation energy burden (i.e. percentage of income spent on vehicle fuels). Excluded in the analysis is the purchase cost of the vehicles themselves. The results reveal that over 90% of vehicle-owning U.S. households would see reductions in both GHGs and transportation energy burden by adopting an EV. For 60% of households these savings would be moderate to high (i.e. >2.3 metric tons of CO2e reduction per household annually and >0.6% of energy burden reduction). These reductions are especially pronounced in the American West (e.g. California, Washington) and parts of the Northeast (e.g. New York) primarily due to a varying combination of cleaner electricity grids, lower electricity prices (relative to gas prices), and smaller drive-cycle and temperature-related impacts on fuel efficiency. Moreover, adopting an EV would more than double the percentage of households that enjoy a low transportation energy burden (<2% of income spent on fuel annually). This equates to 80% of all vehicle-owning U.S. households. Nevertheless, over half of the lowest income households would still have a high EV energy burden (>4% income spent on fuel annually), and if at-home charging is unavailable, this rises to over 75 percent. Addressing this inequity hinges on three major interventions: 1) targeted policies to promote energy justice in lower-income communities, including subsidizing charging infrastructure; 2) strategies to reduce electricity costs; and 3) expanding access to low-carbon transport infrastructure (e.g. public transit, biking, and car sharing).
Basal body organization and cell geometry during the cell cycle in Tetrahymena thermophila
Authors: Sun Huangqingbo , Soh Adam W. J. , Mitchell Lisa E. , Pearson Chad G. , Murphy Robert F.
Published: January 2023

An automated image analysis pipeline to map cell geometry and basal body organization in the ciliate Tetrahymena thermophila is described. Generative modeling was used to computationally reconstruct cell cycle progression from images of cells at single time points. The results reveal novel aspects of basal body distribution and replication.
Younger facial looks are associate with a lower likelihood of several age-related morbidities in the middle-aged to elderly
Authors: Mekić Selma , Pardo Luba M , Gunn David A , Jacobs Leonie C , Hamer Merel A , Ikram M Arfan , Vinke Eline J , Vernooij Meike W , Haarman Annet E G , Thee Eric F , Vergroesen Joelle E , Klaver Caroline C W , Croll Pauline H , Goedegebure Andre , Trajanoska Katerina , Rivadeneira Fernando , van Meurs Joyce B J , Arshi Banafsheh , Kavousi Maryam , de Roos Emmely W , Brusselle Guy G O , Kayser Manfred  , Nijsten Tamar
Published: January 2023

Background

Looking older for one’s chronological age is associated with a higher mortality rate. Yet it remains unclear how perceived facial age relates to morbidity and the degree to which facial ageing reflects systemic ageing of the human body.

Objectives

To investigate the association between ΔPA and age-related morbidities of different organ systems, where ΔPA represents the difference between perceived age (PA) and chronological age.

Methods

We performed a cross-sectional analysis on data from the Rotterdam Study, a population-based cohort study in the Netherlands. High-resolution facial photographs of 2679 men and women aged 51.5–87.8 years of European descent were used to assess PA. PA was estimated and scored in 5-year categories using these photographs by a panel of men and women who were blinded for chronological age and medical history. A linear mixed model was used to generate the mean PAs. The difference between the mean PA and chronological age was calculated (ΔPA), where a higher (positive) ΔPA means that the person looks younger for their age and a lower (negative) ΔPA that the person looks older. ΔPA was tested as a continuous variable for association with ageing-related morbidities including cardiovascular, pulmonary, ophthalmological, neurocognitive, renal, skeletal and auditory morbidities in separate regression analyses, adjusted for age and sex (model 1) and additionally for body mass index, smoking and sun exposure (model 2).

Results

We observed 5-year higher ΔPA (i.e. looking younger by 5 years for one’s age) to be associated with less osteoporosis [odds ratio (OR) 0.76, 95% confidence interval (CI) 0.62–0.93], less chronic obstructive pulmonary disease (OR 0.85, 95% CI 0.77–0.95), less age-related hearing loss (model 2; B = −0.76, 95% CI −1.35 to −0.17) and fewer cataracts (OR 0.84, 95% CI 0.73–0.97), but with better global cognitive functioning (g-factor; model 2; B = 0.07, 95% CI 0.04–0.10).

Conclusions

PA is associated with multiple morbidities and better cognitive function, suggesting that systemic ageing and cognitive ageing are, to an extent, externally visible in the human face.
Management of patients with hidradenitis suppurativa having underlying genetic variation: a systematic review and a call for precision medicine
Authors: Mintoff Dillon , Pace Nikolai P , Borg Isabella
Published: January 2023

Hidradenitis suppurativa (HS) is a chronic inflammatory condition of the pilosebaceous unit characterized by inflammation and hyperkeratinization. A small but significant proportion of patients with HS have a strong genetic susceptibility to (or a syndromic form of) the disease. Current HS treatment guidelines prioritize patients who manifest classic HS and may therefore not be suitable for the minority of patients harbouring genetically driven forms of disease. In this manuscript, we review the extant literature with regards to therapeutic strategies used for patients with HS having disease-associated genetic variants and syndromic forms of the condition. The findings of this review suggest that patients with HS harbouring underlying genetic variants may not be adequately represented in current European and British HS treatment guidelines. Moreover, these patients may be less responsive to the recommended therapeutic options. We therefore make recommendations for future therapeutic guidelines to incorporate considerations for the management of this patient subset.
Review of dermatofibrosarcoma protuberans
Authors: Lim Su X , Ramaiya Arjun , Levell Nick J , Venables Zoe C
Published: January 2023

The clinical features, histological subtypes and management of dermatofibrosarcoma protuberans (DFSP) are reviewed in this article. DFSP is an uncommon cutaneous sarcoma first described in 1890. It has a high local recurrence rate, low metastatic rate and low mortality. The crude incidence rate in England in 2019 was reported as 3.0 per million person-years. A fusion of platelet-derived growth factor subunit B (PDGFB) and COL1A1, t(17;22)(q22;q13), has been found in over 90% of people with DFSP. This fusion is thought to upregulate PDGFB expression, stimulating cell growth by activation of Ras mitogen-activated protein kinases and PI3K–AKT–mTOR, potentiating oncogenesis. DFSP usually presents as an asymptomatic flesh-coloured, thickened, rubbery plaque or nodule with an uneven surface. The most common sites are the trunk followed by lower limbs, head and neck and upper limbs. Larger tumours can infiltrate underlying local structures and around 1% metastasize. Key histological features in DFSP are spindle cells arranged in a storiform pattern with intense CD34 staining. Histological subtypes include classical DFSP, Bednar, myxoid, giant cell fibroblastoma, atrophic and DFSP–fibrosarcomatous. The gold standard management for localized tumours is surgical: current recommendations favour Mohs micrographic surgery over wide local excision. Adjuvant radiotherapy may be offered after surgery. Imatinib can be used as neoadjuvant therapy and in patients with inoperable or metastatic tumours. Further research should be conducted to better understand pathogenesis of DFSP, identify associated risk factors and standardize management.
Individual-level functional connectomes predict the motor symptoms of Parkinson’s disease
Authors: Shi Zhongyan , Jiang Bo , Liu Tiantian , Wang Li , Pei Guangying , Suo Dingjie , Zhang Jian , Funahashi Shintaro , Wu Jinglong , Yan Tianyi
Published: January 2023

Abnormalities in functional connectivity networks are associated with sensorimotor networks in Parkinson’s disease (PD) based on group-level mapping studies, but these results are controversial. Using individual-level cortical segmentation to construct individual brain atlases can supplement the individual information covered by group-level cortical segmentation. Functional connectivity analyses at the individual level are helpful for obtaining clinically useful markers and predicting treatment response. Based on the functional connectivity of individualized regions of interest, a support vector regression model was trained to estimate the severity of motor symptoms for each subject, and a correlation analysis between the estimated scores and clinical symptom scores was performed. Forty-six PD patients aged 50–75 years were included from the Parkinson’s Progression Markers Initiative database, and 63 PD patients were included from the Beijing Rehabilitation Hospital database. Only patients below Hoehn and Yahr stage III were included. The analysis showed that the severity of motor symptoms could be estimated by the individualized functional connectivity between the visual network and sensorimotor network in early-stage disease. The results reveal individual-level connectivity biomarkers related to motor symptoms and emphasize the importance of individual differences in the prediction of the treatment response of PD.
Dissociable salience and default mode network modulation in generalized anxiety disorder: a connectome-wide association study
Authors: Li Rong , Shen Fei , Sun Xiyue , Zou Ting , Li Liyuan , Wang Xuyang , Deng Chijun , Duan Xujun , He Zongling , Yang Mi , Li Zezhi , Chen Huafu
Published: January 2023

Generalized anxiety disorder (GAD) is a common anxiety disorder experiencing psychological and somatic symptoms. Here, we explored the link between the individual variation in functional connectome and anxiety symptoms, especially psychological and somatic dimensions, which remains unknown. In a sample of 118 GAD patients and matched 85 healthy controls (HCs), we used multivariate distance-based matrix regression to examine the relationship between resting-state functional connectivity (FC) and the severity of anxiety. We identified multiple hub regions belonging to salience network (SN) and default mode network (DMN) where dysconnectivity associated with anxiety symptoms (P < 0.05, false discovery rate [FDR]-corrected). Follow-up analyses revealed that patient’s psychological anxiety was dominated by the hyper-connectivity within DMN, whereas the somatic anxiety could be modulated by hyper-connectivity within SN and DMN. Moreover, hypo-connectivity between SN and DMN were related to both anxiety dimensions. Furthermore, GAD patients showed significant network-level FC changes compared with HCs (P < 0.01, FDR-corrected). Finally, we found the connectivity of DMN could predict the individual psychological symptom in an independent GAD sample. Together, our work emphasizes the potential dissociable roles of SN and DMN in the pathophysiology of GAD’s anxiety symptoms, which may be crucial in providing a promising neuroimaging biomarker for novel personalized treatment strategies.
Cortical thickness, gray matter volume, and cognitive performance: a crosssectional study of the moderating effects of age on their interrelationships
Authors: de Chastelaine Marianne , Srokova Sabina , Hou Mingzhu , Kidwai Ambereen , Kafafi Seham S , Racenstein Melanie L , Rugg Michael D
Published: January 2023

In a sample comprising younger, middle-aged, and older cognitively healthy adults (N = 375), we examined associations between mean cortical thickness, gray matter volume (GMV), and performance in 4 cognitive domains—memory, speed, fluency, and crystallized intelligence. In almost all cases, the associations were moderated significantly by age, with the strongest associations in the older age group. An exception to this pattern was identified in a younger adult subgroup aged <23 years when a negative association between cognitive performance and cortical thickness was identified. Other than for speed, all associations between structural metrics and performance in specific cognitive domains were fully mediated by mean cognitive ability. Cortical thickness and GMV explained unique fractions of the variance in mean cognitive ability, speed, and fluency. In no case, however, did the amount of variance jointly explained by the 2 metrics exceed 7% of the total variance. These findings suggest that cortical thickness and GMV are distinct correlates of domain-general cognitive ability, that the strength and, for cortical thickness, the direction of these associations are moderated by age, and that these structural metrics offer only limited insights into the determinants of individual differences in cognitive performance across the adult lifespan.
US–China Economic Rivalry and the Reshoring of Global Supply Chains
Authors: Gur Nurullah , Dilek Serif
Published: January 2023

Since the Global Financial Crisis (GFC) of 2008, the USA has changed its economic priorities and policy preferences in a concerted effort to bolster its weight in the global economy, reduce over-reliance on global supply chains, and create more employment within its borders. This change has become more apparent in the wake of the Trump presidency and the COVID-19 pandemic. Reviving the manufacturing industry through reshoring is now the main goal of US politicians. This article analyses the two strategies, in light of heightened technological competition with China, that the USA has brought into effect to reshore its factories from the People's Republic of China and so revitalise the American manufacturing industry. They are neo-protectionism and smart automation. Arguing that neo-protectionist policies and smart automation technologies are interrelated factors that have been used strategically to bring American multinational companies in China back to the USA, we examine whether or not these two strategies—each elements of the US–China tech war—can support the reshoring and revitalisation of the American manufacturing industry. We find that increased neo-protectionist measures and proliferation of smart automation technologies alone will not empower the USA sufficiently to consolidate its technological superiority over China, add impetus to its manufacturing investments, and create well-paying jobs for the broader segments of American society through the reshoring of manufacturing activities. To achieve these goals, the USA should instead implement an integrated policy framework that spans industrial policies to technology policies and tax policies to labour market policies. Otherwise, even though reshoring may gain a certain momentum, new industrial facilities will not expand productivity enough to raise the competitiveness of the US economy to satisfactory levels, and such investments might not provide enough new job opportunities to remediate socioeconomic problems.
Masking the Strangulation of Opposition Parties as Pandemic Response: Austerity Measures Targeting the Local Level in Hungary
Authors: Kovarek Daniel , Dobos Gábor
Published: January 2023

While a large literature studies the various tools of autocratic survival, targeting opposition actors with austerity measures in electoral autocracies is hitherto understudied. This paper argues that the COVID-19 pandemic has provided a rare opportunity for Hungary’s Fidesz party to disarm opposition parties via cutting off resources of municipalities led by opposition mayors and eliminating any remnants of local governments’ fiscal autonomy. Analysing original data from government decrees on local transfers, this study contributes to the existing literature by conceptualising fiscal strangulation as part of electoral authoritarian regimes’ toolbox to discredit opposition parties and their ability to govern locally.
The Climatic Variability Hypothesis and trade-offs in thermal performance in coastal and inland populations ofMimulus guttatus
Authors: Chiono Alec , Paul John R
Published: January 2023

Ecologists and evolutionary biologists have long predicted that organisms in more climatically variable environments should be adapted to handle a wider range of conditions. This intuitive idea, known as the Climatic Variability Hypothesis (CVH), has gained mixed support from empirical studies. We tested the CVH in a novel system by comparing the thermal breadth of coastal and inland populations of Mimulus guttatus. To quantify thermal breadth, we performed a thermal performance experiment and built performance curves. Using these performance curves, we also evaluated evidence for a breadth-performance trade-off and the Hotter-is-Better hypothesis. We did not find support for the CVH; coastal and inland populations did not differ in thermal breadth. However, we found evidence for a breadth-performance trade-off and the Hotter-is-Better hypothesis. Surprisingly, the two most inland populations differed the most in the thermal performance traits we evaluated. Our results highlight the importance of explicitly measuring thermal performance to test explanations of species distribution patterns and the need to examine alternative mechanisms by which organisms occupy different climatic regimes.
Microbial ecology of vertebrate decomposition in terrestrial ecosystems
Authors: Mason Allison R , Taylor Lois S , DeBruyn Jennifer M
Published: January 2023

Vertebrate decomposition results in an ephemeral disturbance of the surrounding environment. Microbial decomposers are recognized as key players in the breakdown of complex organic compounds, controlling carbon and nutrient fate in the ecosystem and potentially serving as indicators of time since death for forensic applications. As a result, there has been increasing attention on documenting the microbial communities associated with vertebrate decomposition, or the ‘necrobiome’. These necrobiome studies differ in the vertebrate species, microhabitats (e.g. skin vs. soil), and geographic locations studied, but many are narrowly focused on the forensic application of microbial data, missing the larger opportunity to understand the ecology of these communities. To further our understanding of microbial dynamics during vertebrate decomposition and identify knowledge gaps, there is a need to assess the current works from an ecological systems perspective. In this review, we examine recent work pertaining to microbial community dynamics and succession during vertebrate (human and other mammals) decomposition in terrestrial ecosystems, through the lens of a microbial succession ecological framework. From this perspective, we describe three major microbial microhabitats (internal, external, and soil) in terms of their unique successional trajectories and identify three major knowledge gaps that remain to be addressed.
The first gapless, reference-quality, fully annotated genome from a Southern Han Chinese individual
Authors: Chao Kuan-Hao , Zimin Aleksey V , Pertea Mihaela , Salzberg Steven L
Published: January 2023

We used long-read DNA sequencing to assemble the genome of a Southern Han Chinese male. We organized the sequence into chromosomes and filled in gaps using the recently completed T2T-CHM13 genome as a guide, yielding a gap-free genome, Han1, containing 3,099,707,698 bases. Using the T2T-CHM13 annotation as a reference, we mapped all genes onto the Han1 genome and identified additional gene copies, generating a total of 60,708 putative genes, of which 20,003 are protein-coding. A comprehensive comparison between the genes revealed that 235 protein-coding genes were substantially different between the individuals, with frameshifts or truncations affecting the protein-coding sequence. Most of these were heterozygous variants in which one gene copy was unaffected. This represents the first gene-level comparison between two finished, annotated individual human genomes.
One-carbon metabolic enzymes are regulated during cell division and make distinct contributions to the metabolome and cell cycle progression in Saccharomyces cerevisiae
Authors: Hammer Staci E , Polymenis Michael
Published: January 2023

Enzymes of one-carbon (1C) metabolism play pivotal roles in proliferating cells. They are involved in the metabolism of amino acids, nucleotides, and lipids and the supply of all cellular methylations. However, there is limited information about how these enzymes are regulated during cell division and how cell cycle kinetics are affected in several loss-of-function mutants of 1C metabolism. Here, we report that the levels of the S. cerevisiae enzymes Ade17p and Cho2p, involved in the de novo synthesis of purines and phosphatidylcholine (PC), respectively, are cell cycle-regulated. Cells lacking Ade17p, Cho2p, or Shm2p (an enzyme that supplies 1C units from serine) have distinct alterations in size homeostasis and cell cycle kinetics. Loss of Ade17p leads to a specific delay at START, when cells commit to a new round of cell division, while loss of Shm2p has broader effects, reducing growth rate. Furthermore, the inability to synthesize PC de novo in cho2Δ cells delays START and reduces the coherence of nuclear elongation late in the cell cycle. Loss of Cho2p also leads to profound metabolite changes. Besides the expected changes in the lipidome, cho2Δ cells have reduced levels of amino acids, resembling cells shifted to poorer media. These results reveal the different ways that 1C metabolism allocates resources to affect cell proliferation at multiple cell cycle transitions.
Synaptogenesis: unmasking molecular mechanisms using Caenorhabditis elegans
Authors: Mizumoto Kota , Jin Yishi , Bessereau Jean-Louis
Published: January 2023

The nematode Caenorhabditis elegans is a research model organism particularly suited to the mechanistic understanding of synapse genesis in the nervous system. Armed with powerful genetics, knowledge of complete connectomics, and modern genomics, studies using C. elegans have unveiled multiple key regulators in the formation of a functional synapse. Importantly, many signaling networks display remarkable conservation throughout animals, underscoring the contributions of C. elegans research to advance the understanding of our brain. In this chapter, we will review up-to-date information of the contribution of C. elegans to the understanding of chemical synapses, from structure to molecules and to synaptic remodeling.
Context Matters: Health Sensitivity in the Daily Lives of Older Adults Living Through the COVID-19 Pandemic
Authors: Potter Sophie , Duezel Sandra , Demuth Ilja , Gerstorf Denis , Drewelies Johanna
Published: January 2023

Objectives

Throughout 2021, the coronavirus disease (COVID-19) pandemic caused renewed restrictions across Germany. Given the growing evidence that the pandemic negatively affects older adults’ health and well-being, this study investigated health sensitivity (emotional reactions to momentary health challenges) and its moderators (age, morbidity, perceived COVID-19 risks and worries) among older adults in their everyday lives during the second and third waves of the pandemic.

Methods

Multilevel models were applied to self-reported momentary health and affect data, collected 6 times per day across 7 consecutive days in 104 participants (Mage = 76.35; range: 67–88 years), assessed between April and June 2021 (~300,000 COVID-19 cases in Germany at the time).

Results

Health sensitivity was unrelated to age and lower with higher morbidity. Importantly, older adults showed higher health sensitivity in moments when they also perceived a greater risk of contracting COVID-19.

Discussion

Findings suggest that sociocontextual factors related to the pandemic modulate emotional reactions to momentary health challenges, thereby underscoring the consequences of COVID-19 for older adults’ emotional experiences.
Changes in Self-Perceptions of Aging Among Black and White Older Adults: The Role of Volunteering
Authors: Huo Meng , Kim Kyungmin , Haghighat Misha D
Published: January 2023

Objectives

Given the health consequences of self-perceptions of aging (SPA), understanding how SPA change among Black and White older adults may shed light on racial disparities in late-life health. The current study is the first to assess whether Black older adults exhibit less favorable patterns of change in SPA than White older adults. We also tested whether the salubrious effect of volunteering on SPA would be particularly salient among Black older adults.

Methods

A pooled sample of adults aged 50+ (N = 10,183; Black: n = 1,672, White: n = 8,511) from the Health and Retirement Study rated positive and negative SPA once every 4 years across 3 waves (2008/2010, 2012/2014, and 2016/2018). We assessed participants’ reports on volunteering status in each wave.

Results

Growth curve models revealed that positive SPA decreased over time whereas negative SPA increased. Black older adults reported more positive and less negative SPA at baseline and flatter time-related changes than their White counterparts. We found that volunteering was significantly associated with more positive and less negative SPA across waves, but this effect was only evident in White older adults.

Discussion

Findings revealed vulnerabilities in White older adults as they experience and perceive age-related changes but also identified volunteering as a way to uniquely protect them. More research is needed to refine our understanding of racial disparities in the United States and help tailor interventions intended to maximize benefits to older adults from diverse backgrounds.
Genistein Inhibits Clostridioides difficile Infection via Estrogen Receptors and Lysine-Deficient Protein Kinase 1
Authors: Xie Ying , Fontenot Lindsey , Estrada Andrea Chupina , Nelson Becca , Bullock Ashlen , Faull Kym F , Feng Hanping , Sun Mingjun , Koon Hon Wai
Published: January 2023

Background

Clostridioides difficile infection (CDI) is a debilitating nosocomial disease. Postmenopausal women may have an increased risk of CDI, suggesting estrogen influence. Soybean products contain a representative estrogenic isoflavone, genistein.

Methods

The anti-inflammatory and antiapoptotic effects of genistein were determined using primary human cells and fresh colonic tissues. The effects of oral genistein therapy among mice and hamsters were evaluated.

Results

Within 10 days of CDI, female c57BL/6J mice in a standard environment (regular diet) had a 50% survival rate, while those with estrogen depletion and in an isoflavone-free environment (soy-free diet) had a 25% survival rate. Oral genistein improved their 10-day survival rate to 100% on a regular diet and 75% in an isoflavone-free environment. Genistein reduced macrophage inflammatory protein-1α (MIP-1α) secretion in fresh human colonic tissues exposed to toxins. Genistein inhibited MIP-1α secretion in primary human peripheral blood mononuclear cells, abolished apoptosis and BCL-2–associated X (BAX) expression in human colonic epithelial cells, and activated lysine-deficient protein kinase 1 (WNK1) phosphorylation in both cell types. The anti-inflammatory and antiapoptotic effects of genistein were abolished by inhibiting estrogen receptors and WNK1.

Conclusions

Genistein reduces CDI disease activity by inhibiting proinflammatory cytokine expression and apoptosis via the estrogen receptor/G-protein estrogen receptor/WNK1 pathways.
Predicting the metabolizable energy and metabolizability of gross energy of conventional feedstuffs for Muscovy duck using in vitro digestion method
Authors: Wang Heng , Wang Xuyang , Zhan Yuchun , Peng Bin , Wang Wence , Yang Lin , Zhu Yongwen
Published: January 2023

In total, two experiments were conducted to evaluate the effectiveness of an in vitro digestion method for predicting the metabolizable energy (ME) and metabolizability of gross energy (ME/GE) values using in vitro digestible energy (IVDE) and the digestibility of gross energy (IVDE/GE) content, respectively, of conventional feedstuffs for Muscovy ducks. In experiment 1, the apparent metabolizable energy (AME), true metabolizable energy (TME), AME/GE, and TME/GE of eight-grain feedstuff samples (two corn samples, three sorghum samples, and three barley samples) and eight protein feedstuff samples (two soybean meal samples, three cottonseed meal samples, and three rapeseed meal samples) were determined by the tube-feeding method with six different ducks for each sample. In experiment 2, a computer-controlled simulated digestion system (CCSDS) contain simulated digestive fluid was used to determine the enzymatic hydrolysis energy value of feedstuffs, which was defined as IVDE in our study. The simulated gastric fluid containing pepsin and simulated small intestinal fluid containing amylase, trypsin, and chymotrypsin for the in vitro gastric and intestinal digestion, respectively. The IVDE and in vitro digestibility of GE (IVDE/GE) of 16 feedstuff samples were determined using the CCSDS with five replicates per sample. The results showed that the IVDE and IVDE/GE were positively correlated with ME and ME/GE of feedstuffs, respectively. The coefficient of determination of eight regression models in predicting ME (grain feedstuffs: AME = 1.050 × IVDE− 0.9293, TME = 1.032 × IVDE + 0.6478; protein feedstuffs: AME = 1.331 × IVDE− 6.685, TME = 1.269 × IVDE−3.490) and ME/GE (grain feedstuffs: AME/GE = 1.069 × IVDE/GE− 6.516, TME/GE = 1.068 × IVDE/GE + 0.7764; protein feedstuffs: AME/GE = 1.093 × IVDE/GE −19.21, TME/GE = 1.196 × IVDE/GE − 13.25) of feedstuffs for Muscovy ducks ranged from 0.8610 to 0.9921. The accuracy of the regression model was acceptable as the difference between measured and predicted ME and ME/GE values was less than 0.45 MJ/kg (100 kcal/kg) and 2.62% for 14 of the 16 feed samples, respectively. In conclusion, the in vitro digestion method can be used to predict the ME and ME/GE of conventional feedstuffs for Muscovy ducks with acceptable accuracy.
Maintaining Relevance in a Much-Changed World: Reforming WTO Dispute Settlement
Authors: Hughes Valerie
Published: January 2023

The World Trade Organization (WTO) and its dispute settlement mechanism were established in 1995 to great acclaim. Both have seen much success: WTO membership expanded apace, and the WTO dispute settlement mechanism proved to be the most active state-to-state dispute settlement mechanism in history. However, in recent years, the WTO has come under increasing criticism as negotiations to expand and modernize WTO disciplines have produced limited results and dissatisfaction with the dispute settlement system on the part of the system’s most active user led to the paralysis of appellate review. Calls for WTO reform have become widespread. At the June 2022 Ministerial Conference, WTO members committed to work toward necessary reform, including by conducting discussions with a view to having a fully and well-functioning dispute settlement system in place by 2024. This is a tall order, given that long-standing efforts to agree on amendments to the dispute settlement system not only failed but also highlighted significant differences in members’ preferred approaches for resolving disputes. In addition, the legal processes required to implement the major change could take years. This paper identifies adjustments to the dispute settlement system that could lead to important efficiencies and that can be effected before the 2024 deadline arrives.
The role of multimodal salvage therapy in the management of recurrent adrenocortical carcinoma
Authors: Kijima Toshiki , Fukuda Shohei , Fukushima Hiroshi , Uehara Sho , Yasuda Yosuke , Yoshida Soichiro , Yokoyama Minato , Matsuoka Yoh , Saito Kazutaka , Fujii Yasuhisa
Published: January 2023

Background

Adrenocortical carcinoma is an aggressive tumor which often recurs despite apparent complete resection. This study assessed the long-term outcomes for patients with recurrent adrenocortical carcinoma after multimodal salvage therapy with chemotherapy, chemoradiotherapy and surgery.

Methods

We retrospectively reviewed medical records of patients who had a pathological diagnosis of adrenocortical carcinoma between 1996 and 2017. Kaplan–Meier curves were used to assess progression-free and cancer-specific survivals among all patients and cancer-specific survival among patients with tumor recurrence. Log-rank test was used to compare patient survivals by modality of salvage therapy (chemotherapy, chemoradiotherapy and chemotherapy/chemoradiotherapy plus surgery).

Results

Of 20 patients who underwent initial surgery, recurrence occurred in 14 (70%) with a median interval of 7.5 (range 1.0–12.6) months. Salvage therapy provided was chemotherapy only (n = 7), chemoradiotherapy (n = 2) and chemotherapy/chemoradiotherapy plus surgery (n = 5). Of the five patients who received salvage surgery, three underwent repeated resections. The potential benefit of multimodal salvage therapy was suggested in five patients (4 with chemotherapy/chemoradiotherapy plus surgery and 1 with chemoradiotherapy) who achieved durable disease control (cancer-specific survival from initial recurrence, 22–258 months). With a median follow-up of 25 months from recurrence, the 5-year cancer-specific survival rate was 58%. cancer-specific survival after recurrence was prolonged in patients with ≤ stage 3 disease, positive response to chemotherapy/chemoradiotherapy and salvage surgery.

Conclusions

Long-term disease control and survival could be achieved in highly selected patients with recurrent adrenocortical carcinoma using a multidisciplinary approach. Patients who had relatively limited recurrent sites and responded well to chemotherapy/chemoradiotherapy may be considered for salvage surgery on a case-by-case basis.
The conformation of glutenin polymers in wheat grain: some genetic and environmental factors associated with this important characteristic
Authors: Branlard Gérard , d’Orlando Angelina , Tahir Ayesha , Schmutz Marc , Rhazi Larbi , Faye Annie , Aussenac Thierry
Published: January 2023

In a previous study we used asymmetric-flow field-flow fractionation to determine the polymer mass (Mw), gyration radius (Rw) and the polydispersity index of glutenin polymers (GPs) in wheat (Triticum aestivum). Here, using the same multi-location trials (4 years, 11 locations, and 192 cultivars), we report the factors that are associated with the conformation (Conf) of the polymers, which is the slope of Log(Rw) versus a function of Log(Mw). We found that Conf varied between 0.285 and 0.740, it had low broad-sense heritability (H2=16.8), and it was significantly influenced by the temperature occurring over the last month of grain filling. Higher temperatures were found to increase Rw and the compactness and sphericity of GPs. Alleles for both high- and low-molecular-weight glutenin subunits had a significant influence on the Conf value. Assuming a Gaussian distribution for Mw, the number of polymers present in wheat grains was computed for different kernel weights and protein concentrations, and it was found to exceed 1012 GPs per grain. Using atomic force microscopy and cryo-TEM, images of GPs were obtained for the first time. Under higher average temperature, GPs became larger and more spherical and consequently less prone to rapid hydrolysis. We propose some orientations that could be aimed at potentially reducing the impact of numerous GPs on people suffering from non-celiac gluten sensitivity.
SQUAMOSA PROMOTER BINDING PROTEIN-LIKE 9 and 13 repressBLADE-ON-PETIOLE 1and2directly to promote adult leaf morphology in Arabidopsis
Authors: Hu Tieqiang , Manuela Darren , Xu Mingli
Published: January 2023

The juvenile-to-adult phase transition during vegetative development is a critical decision point in a plant’s life cycle. This transition is mediated by a decline in levels of miR156/157 and an increase in the activities of its direct targets, SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (SPL) proteins. In Arabidopsis, the juvenile-to-adult transition is characterized by an increase in the length to width ratio of the leaf blade (a change in the distal region of a leaf), but what mediates this change in lamina shape is not known. Here, we show that ectopic expression of SPL9 and SPL13 produces enlarged and elongated leaves, resembling leaves from the blade-on-petiole1 (bop1) bop2 double mutant. The expression of BOP1/BOP2 is down-regulated in successive leaves, correlating with the amount of miR156 and antagonistic to the expression of SPL9 and SPL13 in leaves. SPL9 and SPL13 bind to the promoters of BOP1/BOP2 directly to repress their expression, resulting in delayed establishment of proliferative regions in leaves, which promotes more blade outgrowth (the distal region of a leaf) and suppresses petiole development (the proximal region of a leaf). Our results reveal a mechanism for leaf development along the proximal–distal axis, a heteroblastic character between juvenile leaves and adult leaves.
Comparative phyloproteomics identifies conserved plasmodesmal proteins
Authors: Johnston Matthew G , Breakspear Andrew , Samwald Sebastian , Zhang Dan , Papp Diana , Faulkner Christine , de Keijzer Jeroen
Published: January 2023

Plasmodesmata are cytosolic bridges, lined by the plasma membrane and traversed by endoplasmic reticulum; plasmodesmata connect cells and tissues, and are critical for many aspects of plant biology. While plasmodesmata are notoriously difficult to extract, tissue fractionation and proteomic analyses can yield valuable knowledge of their composition. Here we have generated two novel proteomes to expand tissue and taxonomic representation of plasmodesmata: one from mature Arabidopsis leaves and one from the moss Physcomitrium patens, and leveraged these and existing data to perform a comparative analysis to identify evolutionarily conserved protein families that are associated with plasmodesmata. Thus, we identified β-1,3-glucanases, C2 lipid-binding proteins, and tetraspanins as core plasmodesmal components that probably serve as essential structural or functional components. Our approach has not only identified elements of a conserved plasmodesmal proteome, but also demonstrated the added power offered by comparative analysis for recalcitrant samples. Conserved plasmodesmal proteins establish a basis upon which ancient plasmodesmal function can be further investigated to determine the essential roles these structures play in multicellular organism physiology in the green lineages.
Scanning Transmission Ion Microscopy Time-of-Flight Spectroscopy Using 20 keV Helium Ions
Authors: Mousley Michael , Tabean Saba , Bouton Olivier , Hoang Quang H , Wirtz Tom , Eswara Santhana
Published: January 2023

Scanning transmission ion microscopy imaging was performed whilst using a delay-line detector to record the impact position and arrival time of transmitted ions or neutrals. The incident helium ion beam had an energy of 20 keV and the arrival time measurements were used to calculate the energy loss after transmission through the sample. The 5D dataset thus produced (2D position in the sample plane, 2D position in the detector plane, and energy) is analyzed by collection into energy spectra or images. It is demonstrated that ion energy loss maps can identify regions of identical materials in the sample plane. The behavior of the energy loss with respect to the scattering angle is calculated and these simulations agree with the experimentally measured results. This experiment demonstrates the capability of keV helium ions to be successfully used in energy loss imaging experiments. This is the first step in the development of keV scanning transmission ion microscopy energy loss techniques.