bluuebunny/crossref_metadata_2025 huggingface dataset:
NUSAP1 Promotes Immunity and Apoptosis by the SHCBP1/JAK2/STAT3 Phosphorylation Pathway to Induce Dendritic Cell Generation in Hepatocellular Carcinoma
Authors: Chen Guojie , Li WenYa , Ge Ruomu , Guo Ting , Zhang Yuhan , Zhou Chenglin , Lin Mei
Published: July 2024

Hepatocellular carcinoma (HCC) is the most common type of liver cancer and is associated with high morbidity and mortality rates. The aims of this study were to investigate the immune-promoting action of nucleolar and spindle-associated protein 1 (NUSAP1) and identify an immunotherapy target for HCC. The Cancer Genome Atlas (TCGA) was used to analyze interaction molecules and immune correlation. The interaction between NUSAP1 and SHC binding and spindle associated 1 (SHCBP1) was examined. The role of the SHCBP1/Janus kinase 2/signal transducer and activator of transcription 3 (SHCBP1/JAK2/STAT3) pathway in this process was explored. After co-culture with HCC cell lines, the differentiation of peripheral blood mononuclear cells (PBMCs) into dendritic cells (DC) was evaluated by measuring the expression of surface factors CD1a and CD86. Pathological tissues from 50 patients with HCC were collected to validate the results of cell experiments. The expression levels of CD1a and CD86 in tissues were also determined. The results show that NUSAP1 interacted with SHCBP1 and was positively correlated with DC. In HCC cell lines, an interaction was observed between NUSAP1 and SHCBP1. It was verified that NUSAP1 inhibited the JAK2/STAT3 phosphorylation pathway by blocking SHCBP1. After co-culture, the levels of CD1a and CD86 in PBMC were elevated. In the clinical specimens, CD1a and CD86 expression levels were significantly higher in the high-NUSAP1 group versus the low-NUSAP1 group. In Summary, NUSAP1 enhanced immunity by inhibiting the SHCBP1/JAK2/STAT3 phosphorylation pathway and promoted DC generation and HCC apoptosis. NUSAP1 may be a target of immunotherapy for HCC.
Clinical Outcomes of Repeat Descemet Membrane Endothelial Keratoplasty After Graft Failure
Authors: Laouani Achraf , Vasiliauskaitė Indrė , Bourgonje Vincent J. A. , Ghaly Mohamed , Lanser Charlotte , van Lieshout Isabel , Baydoun Lamis , Kocaba Viridiana , Melles Gerrit R. J. , Oellerich Silke
Published: July 2024

Purpose:

To evaluate the clinical outcomes after repeat Descemet membrane endothelial keratoplasty (DMEK) for technical failure (TF) and secondary graft failure (SGF).

Methods:

Retrospective analysis of 49 eyes that underwent repeat DMEK either for TF (ie, persistent graft detachment, n = 24) or for SGF (ie, late endothelial graft failure, n = 25). Surgery indications for primary DMEK were Fuchs endothelial corneal dystrophy (FECD, 80%) and bullous keratopathy (BK, 20%). Main outcome measures were best-corrected visual acuity (BCVA), endothelial cell density (ECD), corneal backscattering, pachymetry, and graft survival. Outcomes were compared with an age-matched control group of 49 primary DMEK eyes.

Results:

Logarithm of the minimum angle of resolution BCVA improved from 0.92 ± 0.6 before to 0.20 ± 0.3 at 1 year after repeat DMEK with better outcomes for eyes with TF than those with SGF (P = 0.046). Donor ECD decreased from 2618 ± 171 cells/mm2 before to 1247 ± 422 cells/mm2 at 1 year postoperatively, with no difference between technical TF and SGF eyes (P > 0.05). One-year BCVA and ECD outcomes were better in the control group than in the repeat DMEK group (P < 0.05). Five-year graft survival probability after repeat DMEK was better for TF than for SGF eyes (100% vs. 75%, P = 0.010) and better for eyes with FECD than BK as primary indication for surgery (92% vs. 65%, P = 0.042).

Conclusions:

Repeat DMEK gives acceptable clinical outcomes especially when performed for TF in the early period after primary DMEK. Long-term graft survival probability after repeat DMEK is comparable to primary DMEK for FECD eyes, whereas BK eyes may show an elevated risk to develop graft failure again.
Body Checking Injuries in National Collegiate Athletic Association Men's Ice Hockey: Findings From the NCAA Injury Surveillance Program 2009/10 to 2019/20
Authors: Boltz Adrian J. , Garcia Reagan E. , Alexander Andrew S. , Mihalik Jason P. , Collins Christy L. , Chandran Avinash
Published: July 2024

Objective:

To describe the epidemiology of body checking injuries in the National Collegiate Athletic Association (NCAA) Men's Ice Hockey.

Design:

Secondary data analysis of historical cohort data.

Setting:

A convenience sample of injuries in NCAA Men's Ice Hockey during the 2009/10 to 2019/20 academic years.

Patients (or Participants)

NCAA student-athletes.

Independent Variables:

Event type, season, time loss, body part, diagnosis, player position, and mechanism.

Main Outcome Measures:

This study examined injuries that occurred during practice or competition, regardless of time loss, reported to the NCAA Injury Surveillance Program. Injury counts, rates, and proportions were used. The injury rate and proportion ratios with 95% confidence intervals were also constructed. Three independent logistic regression models were constructed to examine differential odds of time loss (≥1 day; TL) injury and the 2 most common injuries, between body checking injuries and all other injuries.

Results:

Overall, 1290 body checking injuries (rate = 1.59/1000 athlete-exposures) were reported during the study period. Most were attributed to the upper extremity (42%) or head/neck (27%). The competition injury rate generally decreased after 2012/13. After adjusting for covariates, odds of (1) a TL injury was lower and (2) an acromioclavicular sprain was higher among body checking injuries as compared with injuries attributed to all other activities. Odds of concussion was not associated with body checking injuries.

Conclusions:

Body checking injuries were frequently attributed to the head/neck and upper extremities, and the rate of these injuries during competition appeared to be decreasing. Still, improvements in helmet and shoulder pad technology may further improve health and safety.
Vertical Scar Reduction Mammaplasty Using the Superomedial-Based Pedicle Technique in Gigantomastia
Authors: Qiang Shuai , Wang Jia-Yang , Wang Na , Wei Si-Ming , Zhang Zhao-Xiang
Published: July 2024

Background

Breast reduction surgery has witnessed significant advancements in recent years; however, it continues to pose challenges for both surgeons and patients when dealing with cases involving excessive breast volume and severe breast ptosis. This study aimed to assess the aesthetic outcomes and the impact on the quality of life, as measured by the BREAST-Q questionnaire, in patients with gigantomastia and severe breast ptosis who underwent reduction mammaplasty using the superomedial-based pedicle technique.

Methods

We present a retrospective series comprising 84 patients who underwent reduction mammoplasty utilizing the superomedial pedicle technique. The surgical resections exceeded 1 kg per breast, with a mean resection weight of 1506.58 g (right breast) and 1500.32 g (left breast). The preoperative mean suprasternal notch to nipple distance measured 40.50 cm (right breast) and 40.38 cm (left breast). Postoperatively, the patients were followed up for a minimum of 6 months. Both preoperative and postoperative BREAST-Q surveys were administered to the participants, and scores were analyzed using descriptive statistics.

Results

Complications were observed in 3 patients (3.57%), characterized by partial loss of the areola, which resolved spontaneously over time. Additionally, 2 cases of hematoma and 2 instances of minor delayed wound healing were reported. All patients expressed satisfaction with their aesthetic outcomes, as they achieved a natural breast shape and minimal scarring, along with symptomatic relief.

Conclusions

The superomedial pedicle reduction mammaplasty technique has demonstrated its ability to produce satisfactory aesthetic outcomes and long-term benefits in patients with excessively large breasts. Careful patient selection and postoperative management are vital for achieving optimal results. Further investigations involving larger sample sizes and longer follow-up periods are warranted to validate our findings.

Level of Evidence

IV.
Statistical Methods to Examine Racial and Ethnic Disparities in the Surgical Literature
Authors: Harris Alex H.S. , Eddington Hyrum , Shah Vaibhavi B. , Shwartz Michael , Gurewich Deborah , Rosen Amy K. , Quinteros Badí , Wilcher Britni , Nieser Kenneth J. , Jones Gabrielle , Wu Julie Tsu-yu , Morris Arden M.
Published: July 2024

Objective:

To characterize the quality of statistical methods for studies of racial and ethnic disparities in the surgical-relevant literature during 2021-2022.

Background:

Hundreds of scientific papers are published each year describing racial and ethnic disparities in surgical access, quality, and outcomes. The content and design quality of this literature have never been systematically reviewed.

Methods:

We searched for 2021 to 2022 studies focused on describing racial and/or ethnic disparities in surgical or perioperative access, process quality, or outcomes. Identified studies were characterized in terms of 3 methodological criteria: (1) adjustment for variables related to both race/ethnicity and outcomes, including social determinants of health (SDOH), (2) accounting for clustering of patients within hospitals or other subunits (“providers”), and (3) distinguishing within-provider and between-provider effects.

Results:

We identified 224 papers describing racial and/or ethnic differences. Of the 38 single-institution studies, 24 (63.2%) adjusted for at least one SDOH variable. Of the 186 multisite studies, 113 (60.8%) adjusted for at least one SDOH variable, and 43 (23.1%) accounted for the clustering of patients within providers using appropriate statistical methods. Only 10 (5.4%) of multi-institution studies made efforts to examine how much of the overall disparities were driven by within versus between-provider effects.

Conclusions:

Most recently published papers on racial and ethnic disparities in the surgical literature do not meet these important statistical design criteria and, therefore, may risk inaccuracy in the estimation of group differences in surgical access, quality, and outcomes. The most potent leverage points for these improvements are changes to journal publication guidelines and policies.
Acupuncture ameliorates depression-like behavior of poststroke depression model rats through the regulation of gut microbiota and NLRP3 inflammasome in the colon
Authors: Cai Wa , Wei Xi-Fang , Zhang Jing-Ruo , Tao Larissa , Li Dong , Zhang Kun , Shen Wei-Dong
Published: July 2024

This study was conducted to examine the effects of acupuncture on gut microbiota and expression of NLRP3 inflammasome in the colon in poststroke depression (PSD) model rats. Sprague–Dawley male rats were randomized into four groups: sham surgery group, poststroke depression group, acupuncture group, and probiotics group. Acupuncture therapy at Baihui (GV20), Shenting (GV24), bilateral Zusanli (ST36) acupoints in the acupuncture group and probiotic gavage therapy in the probiotics group were performed once per day for 2 weeks. Behaviors of depression were assessed by using weight measurements, sucrose preference test, open field test, and forced swimming test. Histopathological alterations in the colon were determined by hematoxylin–eosin staining, the expression of NLRP3/ASC/caspase-1 pathway-related proteins was analyzed by western blotting. Serum levels of IL-1β and IL-18 were derived from ELISA. The 16S rRNA gene sequencing was performed to examine and analyze the differences of gut microbiota of rats among all groups. Acupuncture was effective to increase weight and ameliorate depressive-like behaviors in PSD rats. Acupuncture increased the diversity of gut microbiota, upregulated the abundance of Bifidobacteriaceae and Lactobacillaceae, and decreased the relative abundance of Peptostreptococcaceae, Rikenellaceae, Eggerthellaceae, and Streptococcaceae at family level. Acupuncture effectively improved the pathological changes in the colon. Meanwhile, acupuncture reduced NLRP3, ASC, caspase-1 protein expressions in the colon, and serum levels of IL-18 and IL-1β. Acupuncture may reduce depressive-like behaviors of PSD by regulating the gut microbiota and suppressing hyperactivation of NLRP3 inflammasome in the colon. Microbiota–gut–brain axis may be an effective target pathway for acupuncture treatment of PSD.
Neural semantic effects of tone accents
Authors: Kwon Jinhee , Roll Mikael
Published: July 2024

This study investigated whether the brain utilizes morphologically induced tones for semantic processing during online speech perception. An auditory comprehension task was conducted while measuring event-related potentials (ERPs). The study tested whether a discrepancy between contextual expectations and the tonal realizations of the target word would yield an N400 effect, indicative of semantic processing difficulty. An N400 effect was observed, reflecting integration difficulty due to semantic anomalies caused by incongruent tones. Additionally, the ERPs in the congruent conditions were modulated by the cohort entropy of the target word indicating lexical competition. The late negativity observed in this study encompasses both the N400 and preactivation negativity. This overlap underscores the brain’s potential for rapidly connecting form and meaning from different sources within the word, relying on statistically based prediction in semantic processing.
Effect of Transcranial Direct Current Stimulation on Craving, Cognitive Functions, and Serum Brain-Derived Neurotrophic Factor Level in Individuals on Maintenance Treatment for Opioid Use Disorder, A Randomized Sham-Controlled Trial
Authors: Borzooee Bahareh , Aghayan Shahrokh , Hassani-Abharian Peyman , Emamian Mohammad Hassan
Published: July 2024

Objectives

To investigate the effects of transcranial direct current stimulation (tDCS) on brain-derived neurotrophic factor (BDNF) levels, craving, and executive functions in individuals on maintenance treatment for opioid use.

Methods

We randomized 70 right-handed men aged 18–55 years into 2 groups: the intervention group and the sham group. The intervention was 10 sessions of 2 mA stimulation over 5 days. Each session in the sham group ended after 30 seconds. Craving was measured using the Desire for Drug Questionnaire (DDQ), Obsessive Compulsive Drug Use Scale (OCDUS), and visual analog scale (VAS). The measurements were taken before and after the intervention, as well as 2 months later. BDNF was measured before and after the intervention. Repeated-measures analysis of variance, the generalized estimating equation model, and independent t test were used for data analysis.

Results

The mean differences (95% confidence intervals) in pre and post craving scores in the intervention group were (12.71 [9.10 to 16.32], P = 0.167) for VAS, (1.54 [1.12 to 1.96], P = 0.012) for OCDUS, and (1.71 [1.27 to 2.15], P = 0.125) for DDQ. These measures in the control group were −0.44 (−1.19 to 0.30), 0.01 (−0.21 to 0.23), and 0.126 (−0.11 to 0.36), respectively. BDNF serum levels significantly increased after the intervention (difference, 0.84 [0.69 to 0.99], P < 0.001); however, this change was not significant in the generalized estimating equation model. The effect of tDCS on craving was significant in OCDUS, but not significant in VAS and DDQ.

Conclusions

The tDCS reduces craving and improves executive functions in the short term. BDNF serum level was not associated with tDCS.
A chemo-mechanical constitutive model for muscle activation in bat wing skins
Authors: Skulborstad Alyssa , Goulbourne N. C.
Published: July 2024

Birds, bats and insects have evolved unique wing structures to achieve a wide range of flight capabilities. Insects have relatively stiff and passive wings, birds have a complex and hierarchical feathered structure and bats have an articulated skeletal system integrated with a highly stretchable skin. The compliant skin of the wing distinguishes bats from all other flying animals and contributes to bats’ remarkable, highly manoeuvrable flight performance and high energetic efficiency. The structural and functional complexity of the bat wing skin is one of the least understood although important elements of the bat flight anatomy. The wing skin has two unusual features: a discrete array of very soft elastin fibres and a discrete array of skeletal muscle fibres. The latter is intriguing because skeletal muscle is typically attached to bone, so the arrangement of intramembranous muscle in soft skin raises questions about its role in flight. In this paper, we develop a multi-scale chemo-mechanical constitutive model for bat wing skin. The chemo-mechanical model links cross-bridge cycling to a structure-based continuum model that describes the active viscoelastic behaviour of the soft anisotropic skin tissue. Continuum models at the tissue length-scale are valuable as they are easily implemented in commercial finite element codes to solve problems involving complex geometries, loading and boundary conditions. The constitutive model presented in this paper will be used in detailed finite element simulations to improve our understanding of the mechanics of bat flight in the context of wing kinematics and aerodynamic performance.
Fibroblast-like synoviocytes orchestrate daily rhythmic inflammation in arthritis
Authors: Downton Polly , Dickson Suzanna H. , Ray David W. , Bechtold David A. , Gibbs Julie E.
Published: July 2024

Rheumatoid arthritis is a chronic inflammatory disease that shows characteristic diurnal variation in symptom severity, where joint resident fibroblast-like synoviocytes (FLS) act as important mediators of arthritis pathology. We investigate the role of FLS circadian clock function in directing rhythmic joint inflammation in a murine model of inflammatory arthritis. We demonstrate FLS time-of-day-dependent gene expression is attenuated in arthritic joints, except for a subset of disease-modifying genes. The deletion of essential clock gene
Bmal1
in FLS reduced susceptibility to collagen-induced arthritis but did not impact symptomatic severity in affected mice. Notably, FLS
Bmal1
deletion resulted in loss of diurnal expression of disease-modulating genes across the joint, and elevated production of MMP3, a prognostic marker of joint damage in inflammatory arthritis. This work identifies the FLS circadian clock as an influential driver of daily oscillations in joint inflammation, and a potential regulator of destructive pathology in chronic inflammatory arthritis.
Rodent chronic variable stress procedures: a disjunction between stress entity and impact on behaviour
Authors: Romanò Nicola , Menzies John
Published: July 2024

Chronic variable stress (CVS) procedures are widely used to model depression in laboratory rodents. We systematically documented the experimental design used in mouse CVS studies, and the design of the behavioural tests used to evaluate the effect of CVS. In a subset of studies, we measured effect sizes in behavioural tests. Across 202 mouse studies, 82% used a unique CVS procedure. We took advantage of this variability to ask whether the duration and intensity of CVS procedures correlated with effects sizes obtained in five commonly-used behavioural tests: the sucrose preference test (SPT), the tail suspension test (TST), the forced swim test (FST), the open field test (OFT) and the elevated plus maze (EPM). The most evident impact of CVS procedure design on effect sizes were seen in the FST where longer-duration CVS procedures with more diverse types of stressors were associated with a smaller effect size. Next, we correlated effect sizesbetweenbehavioural tests to explore whether these tests might measure similar or different consequences of CVS. We found a positive correlation between effects sizes in the TST and FST, and in the OFT and EPM, but the two strongest positive correlations were between the EPM and TST, and between the EPM and FST. CVS studies deliberately impose suffering over long periods, and our data raise scientific and ethical questions around the stress procedures used and the behavioural tests used to evaluate them.
Characterizing BOLD activation patterns in the human hippocampus with laminar fMRI
Authors: Pfaffenrot Viktor , Bouyeure Antoine , Gomes Carlos Alexandre , Kashyap Sriranga , Axmacher Nikolai , Norris David G
Published: July 2024

The human hippocampus has been extensively studied at the macroscale using functional magnetic resonance imaging (fMRI) but the underlying microcircuits at the mesoscale (i.e., at the level of layers) are largely uninvestigated in humans. We target two questions fundamental to hippocampal laminar fMRI: How does the venous bias affect the interpretation of hippocampal laminar responses? And can we establish a benchmark laminar fMRI experiment which robustly elicits single-subject hippocampal activation utilizing the most widely applied GRE-BOLD contrast? We comprehensively characterized GRE-BOLD responses as well as T2*, tSNR and physiological noise as a function of cortical depth in individual subfields of the human hippocampus. Our results show that the vascular architecture differs between subfields leading to subfield-specific laminar biases of GRE-BOLD responses. Using an autobiographical memory paradigm, we robustly acquired depth-specific BOLD responses in hippocampal subfields. In the CA1 subregion, our results indicate a more pronounced trisynaptic path input rather than dominant direct inputs from entorhinal cortex during autobiographical memory retrival. Our study provides unique insights into the hippocampus at the mesoscale level, and will help interpreting hippocampal laminar fMRI responses and allow researchers to test mechanistic hypotheses of hippocampal function.
Acidic pH attenuates immune killing through inactivation of perforin
Authors: Hodel Adrian W , Rudd-Schmidt Jesse A , Noori Tahereh , Lupton Christopher J , Cheuk Veronica CT , Trapani Joseph A , Hoogenboom Bart W , Voskoboinik Ilia
Published: July 2024

Cytotoxic lymphocytes are pivotal effectors in our immune system. Their most potent way to delete virus infected or cancerous target cells is by perforin/granzyme dependent killing. Perforin is secreted into the immunological synapse and forms transmembrane pores in the target cell plasma membrane, allowing granzymes to enter the target cell cytosol and trigger apoptosis. The prowess of cytotoxic lymphocytes to efficiently eradicate target cells has been widely harnessed in immunotherapies against haematological cancers. Despite efforts to achieve a similar outcome against solid tumours, the immunosuppressive and acidic tumour microenvironment poses a persistent obstacle. Using different types of effector cells, including therapeutically relevant anti-CD19 CAR T cells, we demonstrate that the acidic pH typically found in solid tumours hinders the efficacy of immune therapies by impeding perforin pore formation within the immunological synapse. Nanometre-scale study of purified recombinant perforin undergoing oligomerization reveals that pore formation is inhibited specifically by preventing the formation of a transmembrane β-barrel. The absence of perforin pore formation directly prevents target cell death. This finding uncovers a novel layer of immune effector inhibition that must be considered in the development of effective immunotherapies for solid tumours.

One Sentence Summary

Our study reveals that an acidic environment hinders the efficacy of immune therapies by impeding the action of perforin, a critical protein in immune-mediated cell killing, directly within the immunological synapse.
Hepatic Nrf1 (Nfe2l1) promotes VLDL dependent liver defense against sepsis
Authors: Trites Michael J. , Li Lei , Akl May G. , Hydomako Aidan , Widenmaier Scott B.
Published: July 2024

Sepsis causes mortality by triggering organ damage. Interest has emerged in stimulating disease tolerance to reduce organ damage. Liver plays a role in disease tolerance by mediating defensive adaptations, but sepsis-induced liver damage limit these effects. Here, we investigated whether stress defending transcription factors nuclear factor erythroid 2 related factor-1 (Nrf1) and -2 (Nrf2) in hepatocytes protect against sepsis. Using mice, we evaluated responses by hepatic Nrf1 and Nrf2 during sepsis triggered by lipopolysaccharide orEscherichia coli. We also genetically altered hepatic Nrf1 and Nrf2 activity to determine the protective role of these factors in sepsis. Our results show hepatic Nrf1 and Nrf2 activity is reduced in severe sepsis and hepatic Nrf1, but not Nrf2, deficiency predisposes for hypothermia and mortality. In contrast, enhancing hepatic Nrf1 activity protects against hypothermia and improves survival. Moreover, in sepsis hepatic Nrf1 deficiency reduces VLDL secretion whereas enhancing hepatic Nrf1 increases VLDL secretion, and inhibiting VLDL secretion with lomitapide obstructs protective actions of hepatic Nrf1. Gene expression profiles suggest Nrf1 promotes this effect by inducing stress defenses. Hence, we show mortality in sepsis may result from impaired stress defense and that hepatic Nrf1 improves disease tolerance during sepsis by promoting VLDL dependent liver defense.
Characterization of theCannabis sativaglandular trichome epigenome
Authors: Conneely Lee J. , Hurgobin Bhavna , Ng Sophia , Tamiru-Oli Muluneh , Lewsey Mathew G.
Published: July 2024

Background

The relationship between epigenomics and plant specialised metabolism remains largely unexplored despite the fundamental importance of epigenomics in gene regulation and, potentially, yield of products of plant specialised metabolic pathways. The glandular trichomes ofCannabis sativaare an emerging model system that produce large quantities of cannabinoid and terpenoid specialised metabolites with known medicinal and commercial value. To address the lack of epigenomic data in plant specialised metabolism, glandular trichomes, andC. sativa, we mapped H3K4 trimethylation, H3K56 acetylation, H3K27 trimethylation post-translational modifications and the histone variant H2A.Z, using chromatin immunoprecipitation, in glandular trichomes, leaf, and stem tissues. Corresponding transcriptomic (RNA-seq) datasets were integrated, and tissue-specific analyses conducted to relate chromatin states to glandular trichome specific gene expression.

Results

Cannabinoid and terpenoid biosynthetic genes, specialised metabolite transporters, and defence related genes, were co-located with distal H3K56ac chromatin, a histone mark that flanks active distal enhancersin planta, exclusively in glandular trichomes. Glandular trichome specific H3K4 trimethylated chromatin was associated with genes involved in specialised metabolism and sucrose and starch metabolism. Bi-valent chromatin loci specific to glandular trichomes, marked with H3K4 trimethylation and H3K27 trimethylation, was associated with genes of MAPK signalling pathways and plant specialised metabolism pathways, supporting recent hypotheses that implicate bi-valent chromatin in plant defence. The histone variant H2A.Z was largely found in intergenic regions and enriched in chromatin that contained genes involved in DNA homeostasis.

Conclusion

We report the first genome-wide histone post-translational modification maps forC. sativaglandular trichomes, and more broadly for glandular trichomes in plants. Our findings have implications in plant adaptation and stress response and provide a basis for enhancer-mediated, targeted, gene transformation studies in plant glandular trichomes.
Effector T cells in poorly perfused tumor regions exhibit a distinct signature of augmented IFN response and reduced PD-1 expression
Authors: Riera-Borrull Marta , Vaquero Sonia Tejedor , Porqueras Víctor Cerdán , Aramburu Jose , López-Rodríguez Cristina
Published: July 2024

Effector T lymphocytes are avid glucose consumers, but can function in the nutrient-poor environments of tumors. However, availability of blood-delivered nutrients throughout the tumor is not homogeneous, and how this affects effector T cells is not well known. Here we have isolated tumor-infiltrating T lymphocytes (TILs) from mouse solid tumors by their capacity to capture blood-transported probes, and compared them with glucose-restricted T cells. Glucose restrictionin vitroarrested cell proliferation but reduced only moderately the induction of hallmark glucose-dependent cytokines interferon gamma (IFNγ) and IL-17.In vivo, effector TILs with reduced access to blood had characteristics of glucose-restricted cells, such as reduced expression of IFNγ and genes associated with cell proliferation. However, they expressed more CXCR3, which identifies effective antitumor T lymphocytes, showed an enhanced IFN response signature, and had reduced expression of surface PD-1. We also identified genes regulated by the enzyme ACSS2, which allows TILs to sustain gene expression in glucose-poor environments. Thus, effector T lymphocytes infiltrating tumors express different gene signatures in regions with different accessibility to blood, and can maintain specific glucose-dependent responses even in poorly perfused tumor regions. Our results can help better understand nutrient-dependent TIL heterogeneity in changing tumor microenvironments.

Abstract Figure
DNA walk of specific fused oncogenes exhibit distinct fractal geometric characteristics in nucleotide patterns
Authors: Das Abhijeet , Sehgal Manas , Singh Ashwini , Goyal Rishabh , Prabhakar Mallika , Fricke Jeremy , Mambetsariev Isa , Kulkarni Prakash , Jolly Mohit Kumar , Salgia Ravi
Published: July 2024

Background/Objectives

The complex system of cancer has led to an emphasis on understanding the more general causal relationship within the disease. In this context, concepts of symmetry and symmetry-breaking in distinct biological cell features or components have been examined as an approach to cancer investigation. However, there can be possible limitations in directly interpreting the symmetry-based approach from a physical viewpoint due to the lack of understanding of physical laws governing symmetry in complex systems like cancer.

Methods

Fractal geometry and DNA walk representation were employed to investigate the geometric features i.e., self-similarity and heterogeneity in DNA nucleotide coding sequences of wild-type and mutated oncogenes, tumour-suppressor, and other unclassified genes. The mutation-facilitated self-similar and heterogenous features were quantified by the fractal dimension and lacunarity coefficient measures, respectively. Additionally, the geometrical orderedness and disorderedness in the analyzed sequences were interpreted from the combination of the fractal measures.

Results

The findings showed distinct fractal geometric features in the case of fusion mutations. It also highlights the possible interpretation of the observed fractal features as geometric analogues concerning explicit observations corresponding to specific cancer types. In addition, the two-dimensional multi-fractal analysis highlighted the presence of a single exponent in the scaling of mutation-mediated gene sequence self-similarity/complexity and heterogeneity.

Conclusions

The approach identified mutation-induced geometric features in gene sequences, demonstrating the potential of DNA walks and fractal analysis in translational research regarding cancer. The findings suggest that investigating fractal parameters can capture unique geometric features in nucleotide sequences, contributing to the understanding of cancer’s molecular complexity.
Landscape conservation and orchard management influence carob tree yield through changes in pollinator communities
Authors: Gómez-Martínez Carmelo , González-Estévez Miguel A. , deCastro-Arrazola Indradatta , Unglaub Peter , Lázaro Amparo
Published: July 2024

Worldwide pollinator declines are a major problem for agricultural production. However, understanding how landscape characteristics and local management influence crop production through its pollinators is still a challenge. By sampling 20 orchards in Mallorca island (Spain), we evaluated how the landscape (habitat loss) and orchard local management (farming system: conventional vs. ecological; male-to-female ratio) influenced pollinator communities and production in carob trees (Ceratonia siliqua), a crop of high economic importance in Mediterranean areas. We found that orchards surrounded by larger natural areas received more visits by wild bees and butterflies and fewer by honeybees. Ecological farming tended to increase overall pollinator abundance in the orchards. High male-to-female ratio enhanced overall pollinator abundance and shaped pollinator composition, by increasing hoverfly abundance and decreasing wasps and flies. Male-to-female ratio showed hump-shaped relationships with fruit and seed production per female tree (peak at 0.7 males/female), whereas total orchard production maximized with 20-30% of males. Seed weight (farmer’s highest economic value) increased in conserved landscapes where wild pollinators prevailed, and with overall pollinator abundance; however, it decreased with male-to-female ratio, likely due to seed number-size trade-offs. Management strategies to enhance carob production may optimize sex ratios and favor wild pollinators by reducing pesticide use and preserving natural landscapes.
TSS-Captur: A User-Friendly Characterization Pipeline for Transcribed but Unclassified RNA transcripts
Authors: Paz Mathias Witte , Vogel Thomas , Nieselt Kay
Published: July 2024

Abstract

RNA-seq and its 5’-enrichment-based methods for prokaryotes have enabled the base-exact identification of transcription starting sites (TSSs) and have improved gene expression analysis. Computational methods analyze this experimental data to identify TSSs and classify them based on proximal annotated genes. While some TSSs cannot be classified at all (orphan TSSs), other TSSs are found on the reverse strand of known genes (antisense TSSs), but are not associated with the direct transcription of any known gene. Here, we introduceTSS-Captur, a novel pipeline, that uses computational approaches to characterize genomic regions starting from experimentally confirmed, but unclassified TSSs. By analyzing experimental TSS data,TSS-Capturcharacterizes unclassified signals, hence complementing prokaryotic genome annotation tools and enhancing the bacterial transcriptome understanding.TSS-Capturclassifies extracted transcripts into coding or non-coding genes and predicts for each putative transcript its transcription termination site. For non-coding genes, the secondary structure is computed. Furthermore, putative promoter regions are analyzed to identify enriched motifs. An interactive report allows a seamless data exploration. We validatedTSS-Capturwith aCampylobacter jejunidataset and characterized unlabeled non-coding RNAs inStreptomyces coelicolor. Besides its usage over the command-line,TSS-Capturis available as a web-application to enhance its user accessibility and explorative capabilities.
Decision-making shapes dynamic inter-areal communication within macaque ventral frontal cortex
Authors: Stoll Frederic M. , Rudebeck Peter H.
Published: July 2024

Macaque ventral frontal cortex is comprised of a set of anatomically heterogeneous and highly interconnected areas. Collectively these areas have been implicated in many higher-level affective and cognitive processes, most notably the adaptive control of decision-making. Despite this appreciation, little is known about how subdivisions of ventral frontal cortex dynamically interact with each other during decision-making. Here we assessed functional interactions between areas by analyzing the activity of thousands of single neurons recorded from eight anatomically defined subdivisions of ventral frontal cortex in macaques performing a visually guided two-choice probabilistic task for different fruit juices. We found that the onset of stimuli and reward delivery globally increased communication between all parts of ventral frontal cortex. Inter-areal communication was, however, temporally specific, occurred through unique activity subspaces between areas, and depended on the encoding of decision variables. In particular, areas 12l and 12o showed the highest connectivity with other areas while being more likely to receive information from other parts of ventral frontal cortex than to send it. This pattern of functional connectivity suggests a role for these two areas in integrating diverse sources of information during decision processes. Taken together, our work reveals the specific patterns of inter-areal communication between anatomically connected subdivisions of ventral frontal cortex that are dynamically engaged during decision-making.
Stat3 mediates Fyn kinase driven dopaminergic neurodegeneration and microglia activation
Authors: Siddiqui Sahiba , Liu Fang , Kanthasamy Anumantha G. , McGrail Maura
Published: July 2024

The Alzheimer’s Disease and Parkinson’s Disease risk locus Fyn kinase is implicated in neurodegeneration and inflammatory signaling. To investigatein vivomechanisms of Fyn driven neurodegeneration, we built a zebrafish neural specific Gal4:UAS model of constitutively active FynY531F signaling. Usingin vivolive imaging we demonstrate neural FynY531F expression lead to dopaminergic neuron loss and mitochondrial aggregation in 5 day larval brain. Dopaminergic loss coincided with microglia activation and induction oftnfa,il1b, andil12ainflammatory cytokine expression. Transcriptome analysis revealed Stat3 signaling as a potential Fyn target. Chemical inhibition experiments confirmed Fyn driven dopaminergic neuron loss and the inflammatory response were dependent upon activation of Stat3 and NF-κB pathways. Dual chemical inhibition demonstrated Stat3 acts synergistically with NF-κB in dopaminergic neuron degeneration. These results identify Stat3 as a novel downstream effector of Fyn signaling in neurodegeneration and inflammation.

Summary Statement

This study describes a novelin vivomodel of neural Fyn Kinase activation and identifies Stat3 signaling as a downstream Fyn effector in dopaminergic neuron degeneration and neuroinflammation.

Abstract Figure

Graphical abstract

- Neural Fyn signaling drives dopaminergic neurodegeneration, mitochondria accumulation, and microglia activation

- Fyn driven neurodegeneration and cytokine expression are dependent on Stat3

- Stat3 and NF-kB pathways synergize in dopaminergic neuron degeneration
Regulation of cell–nanoparticle interactions through mechanobiology
Authors: Cassani Marco , Niro Francesco , Durikova Helena , Morazzo Sofia , Pereira-Sousa Daniel , Fernandes Soraia , Vrbsky Jan , Oliver-De La Cruz Jorge , Klimovic Simon , Pribyl Jan , Loja Tomas , Skladal Petr , Caruso Frank , Forte Giancarlo
Published: July 2024

Bio–nano interactions have been extensively explored in nanomedicine to develop selective delivery strategies, reduce systemic toxicity, and minimize therapeutic dosing requirements. To enhance the delivery of nanocarriers to cancer cells and improve the therapeutic efficiency and clinical translation of nanomedicines, numerous nanomaterials with diverse and tunable properties have been developed. However, the limited clinical translation of nanoparticle-based therapies, largely due to issues associated with poor targeting and therapeutic delivery, requires a deeper understanding of the biological phenomena underlying cell–nanoparticle interactions. In this context, herein we investigate the molecular and cellular mechanobiology parameters that control such interactions. We demonstrate that the pharmacological inhibition or the genetic ablation of the key mechanosensitive component of the Hippo pathway, i.e., yes-associated protein, enhances nanoparticle internalization by 1.5-fold. Importantly, this phenomenon occurs independently of nanoparticle properties, such as size, or cell properties such as surface area, substrate adhesion, and stiffness. Our study reveals that the internalization of nanoparticles in target cells can be controlled by modulating cell mechanosensing pathways, potentially ultimately enhancing nanoparticle delivery and nanotherapy specificity.
Investigating the Efficacy of Ergothioneine to Delay Cognitive Decline in Mild Cognitively Impaired Subjects: A Pilot Study
Authors: Yau Yu Fung , Cheah Irwin K. , Mahendran Rathi , Tang Richard M.Y. , Chua Ru Yuan , Goh Rachel E.S. , Feng Lei , Li Jialiang , Kua Ee Heok , Chen Christopher , Halliwell Barry
Published: July 2024

Background and objective

Dementia, particularly Alzheimer’s disease, is a major healthcare challenge in ageing societies. Therefore, this study aimed to investigate the efficacy and safety of a dietary compound, ergothioneine, in delaying cognitive decline in elderly individuals.

Design, intervention and measurements

Nineteen subjects aged 60 or above with mild cognitive impairment were recruited for this double-blinded, randomized, and placebo- controlled study. Subjects received either ergothioneine (25mg per capsule) or a placebo, taken 3 times a week for one year. The whole blood profile, markers of renal and liver functions, neurocognitive performance, plasma levels of ergothioneine and its metabolites, and plasma biomarkers related to neurodegeneration were measured across the study.

Result

Ergothioneine intake did not alter clinical safety markers (blood counts, kidney and liver function) throughout the study, further validating its safety for human consumption. Subjects receiving ergothioneine demonstrated improved performance in assessment of learning ability and stabilized plasma levels of neurofilament light chain, compared with placebo group which saw no improvement in cognitive assessments and a significant increase in neurofilament light chain.

Conclusion

Prolonged intake of ergothioneine showed no toxicity in elderly individuals. Enhanced Rey Auditory Verbal Learning Test performance and stabilized neurofilament light chain levels suggest improvements in memory and learning abilities, alongside a deceleration of neuronal damage. Our results add to existing data that ergothioneine is safe for extended consumption and may hold the potential to delay cognitive decline in the elderly.
Non-contact and non-constraining monitoring of the respiratory rate including sleep disordered breathing using ultra-wideband radar
Authors: Kazuo Chin , Shigeaki Okumura , Daisuke Endo , Kazuma Nagata , Tatsuya Ito , Kimihiko Murase , Hironobu Sunadome , Mamiko Hoshi , Hisato Hiranuma , Yutaka Kozu , Susumu Sato , Toyohiro Hirai , Yasuhiro Gon , Takuya Sakamoto , Hirofumi Taki , Toshiki Akahoshi
Published: July 2024

Background

The respiratory rate (RR) is a critical vital sign controlled by not only metabolic factors but behavior while awake. The prevalence of obstructive sleep apnea (OSA) is remarkably high. Therefore, a non-constraining and non-contact respiratory monitor to measure the RR both while awake and asleep is preferable.

Methods

A millimeter wave radar (MWR) device was used for RR monitoring of participants suspected of OSA while awake (supine before and after polysomnography [PSG], sitting, and positioned on both sides) and asleep. Apnea and hypopnea during 1 hour of sleep (AHI) by PSG was compared with 1 hour of respiratory events (REI) judged by MWR. Portable monitoring (PM) and percutaneous arterial O2(SpO2) monitoring were done simultaneously.

Results

Correlations between the RR by MWR and respiratory inductance plethysmography at PSG while awake in every measured position including the supine position before and after PSG were very high (r=0.92∼0.99) (n=60). The REI by MWR were significantly correlated with AHI determined by PSG, PM, or SpO2monitoring (p<0.001). Brand-Altman plot showed that the MWR for AHI monitoring was acceptable. Predicted AHI by MWR relative to PSG was almost the same as with PM or SpO2monitoring.

Conclusions

The developed MWR respiratory monitor was useful during wakefulness and sleep, including detection of apnea and hypopnea. This system can be useful in multiple medical settings such as critical care with and without sleep apnea, pandemic infection, elder care at home, etc. Trial registration number: UMIN000045833 (http://www.umin/ac.jp)
Typing of feces-derivedCandida albicansstrains using a novel seven-locus microsatellite panel reveals associations with yeast phenotype in individuals with inflammatory bowel disease
Authors: van Thiel Isabelle A.M. , Kreulen Irini A.M. , Bénard Mèlanie V. , de Goffau Marcus C. , Theelen Bart , Heinsbroek Sigrid E.M. , Zylka Patrycja K. , Ponsioen Cyriel Y. , Boekhout Teun , de Jonge Wouter J. , Rosendahl Søren , van den Wijngaard René M. , Hagen Ferry
Published: July 2024

Inflammatory diseases of the human gastrointestinal tract are affected by the microbes that reside in the mucosal surfaces along this tract. Patients with inflammatory bowel diseases (IBD) have altered bacterial and fungal intestinal compositions, including higher levels of fecalCandidayeasts. Ongoing research indicates that genetic and phenotypic diversity ofCandida albicansmay be linked with disease severity. In this study, we set out to investigate feces-derivedC. albicansstrains from individuals with Crohn’s disease, ulcerative colitis, and healthy volunteers through microsatellite-based genotyping and phenotypic assays. A seven-locus microsatellite panel was applied, of which six loci were newly developed. Combined interpretation of minimum spanning networks and principal component analysis (PCA) led to indications that there is no specific lineage ofC. albicansthat is associated with IBD, but rather that the three study populations do have distinguishable distributions of genotypes. In addition, phenotypic characterization by means of enzyme release assays revealed trends between genotypes and virulence-related enzyme activity. Furthermore, correlations were observed between the clinical inflammation biomarker fecal calprotectin and serum anti-Saccharomyces cerevisiaeantibodies, as well as between lipase activity of feces-derivedC. albicansstrains and serum 1,3-β-glucan levels. We thus show that microsatellite typing can describe genetic diversity of feces-derivedC. albicansstrains, and that phenotypic diversity of these strains may indeed correlate with fungal genotype or disease. This study opens further possibilities to investigate fecal fungi in relation to severity of inflammation in IBD or in other (intestinal) diseases.
Tabula Glycine: The whole-soybean single-cell resolution transcriptome atlas
Authors: Cervantes-Pérez Sergio Alan , Thibivilliers Sandra , Amini Sahand , Pelletier Julie M. , Meyer Ian , Xu Hengping , Tennant Sutton , Ma Pengchong , Sprueill Chandler M. , Farmer Andrew D. , Coate Jeremy E. , Nelissen Hilde , Yao Qiuming , Martin Olivier C. , Amézquita Erik J. , Goldberg Robert B. , Harada John J. , Libault Marc
Published: July 2024

Soybean (Glycine max) is an essential source of protein and oil with high nutritional value for human and animal consumption. To enhance our understanding of soybean biology, it is essential to have accurate information regarding the expression of each of its 55,897 protein-coding genes. Here, we present “Tabula Glycine”, the soybean single-cell resolution transcriptome atlas. This atlas is composed of single-nucleus RNA-sequencing data of nearly 120,000 nuclei isolated from 10 differentGlycine maxorgans and morphological structures comprising the entire soybean plant. These nuclei are grouped into 157 different clusters based on their transcriptomic profiles. Among genes, the pattern of activity of transcription factor genes is sufficient to define most cell types and their organ/morphological structure of origin, suggesting that transcription factors are key determinants of cell identity and function. This unprecedented level of resolution makes the Tabula Glycine a unique resource for the plant and soybean communities.