bluuebunny/crossref_metadata_2025 huggingface dataset:
Keeping the balance: Trade-offs between human brain evolution, autism, and schizophrenia
Authors: Duński Eryk , Pękowska Aleksandra
Published: November 2022

The unique qualities of the human brain are a product of a complex evolutionary process. Evolution, famously described by François Jacob as a “tinkerer,” builds upon existing genetic elements by modifying and repurposing them for new functions. Genetic changes in DNA may lead to the emergence of new genes or cause altered gene expression patterns. Both gene and regulatory element mutations may lead to new functions. Yet, this process may lead to side-effects. An evolutionary trade-off occurs when an otherwise beneficial change, which is important for evolutionary success and is under strong positive selection, concurrently results in a detrimental change in another trait. Pleiotropy occurs when a gene affects multiple traits. Antagonistic pleiotropy is a phenomenon whereby a genetic variant leads to an increase in fitness at one life-stage or in a specific environment, but simultaneously decreases fitness in another respect. Therefore, it is conceivable that the molecular underpinnings of evolution of highly complex traits, including brain size or cognitive ability, under certain conditions could result in deleterious effects, which would increase the susceptibility to psychiatric or neurodevelopmental diseases. Here, we discuss possible trade-offs and antagonistic pleiotropies between evolutionary change in a gene sequence, dosage or activity and the susceptibility of individuals to autism spectrum disorders and schizophrenia. We present current knowledge about genes and alterations in gene regulatory landscapes, which have likely played a role in establishing human-specific traits and have been implicated in those diseases.
Multilevel view on chromatin architecture alterations in cancer
Authors: Gridina Maria , Fishman Veniamin
Published: November 2022

Chromosomes inside the nucleus are not located in the form of linear molecules. Instead, there is a complex multilevel genome folding that includes nucleosomes packaging, formation of chromatin loops, domains, compartments, and finally, chromosomal territories. Proper spatial organization play an essential role for the correct functioning of the genome, and is therefore dynamically changed during development or disease. Here we discuss how the organization of the cancer cell genome differs from the healthy genome at various levels. A better understanding of how malignization affects genome organization and long-range gene regulation will help to reveal the molecular mechanisms underlying cancer development and evolution.
LncRNAs-associated to genomic instability: A barrier to cancer therapy effectiveness
Authors: Andonegui-Elguera Marco A , Cáceres-Gutiérrez Rodrigo E. , Oliva-Rico Diego , Díaz-Chávez José , Herrera Luis A.
Published: November 2022

Although a large part of the genome is transcribed, only 1.9% has a protein-coding potential; most of the transcripts are non-coding RNAs such as snRNAs, tRNAs, and rRNAs that participate in mRNA processing and translation. In addition, there are small RNAs with a regulatory role, such as siRNAs, miRNAs, and piRNAs. Finally, the long non-coding RNAs (lncRNAs) are transcripts of more than 200 bp that can positively and negatively regulate gene expression (both in cis and trans), serve as a scaffold for protein recruitment, and control nuclear architecture, among other functions. An essential process regulated by lncRNAs is genome stability. LncRNAs regulate genes associated with DNA repair and chromosome segregation; they are also directly involved in the maintenance of telomeres and have recently been associated with the activity of the centromeres. In cancer, many alterations in lncRNAs have been found to promote genomic instability, which is a hallmark of cancer and is associated with resistance to chemotherapy. In this review, we analyze the most recent findings of lncRNA alterations in cancer, their relevance in genomic instability, and their impact on the resistance of tumor cells to anticancer therapy.
Differential diagnosis and identification of prognostic markers for peripheral T-cell lymphoma subtypes based on flow cytometry immunophenotype profiles
Authors: Pu Qiyao , Qiao Jie , Liu Yuke , Cao Xueyan , Tan Ran , Yan Dongyao , Wang Xiaoqian , Li Jiwei , Yue Baohong
Published: November 2022

We compared the differential expression of 15 markers in PTCL (Peripheral T-cell lymphoma) subtypes and T-CUS (T-cell clones of uncertain significance), and summarized the specific immunophenotype profiles of each subtype and its impact on prognosis. PD-1 and CD10 are diagnostic markers for AITL (angioimmunoblastic T-cell lymphoma). To avoid confusion with T-CUS of benign clones, it is recommended to define AITL as bounded by PD-1+%>38.01 and/or CD10+%>7.46. T cell-derived ENKTL-N (extranodal NKT cell lymphoma) specifically expresses CD56. ALCL (anaplastic large cell lymphoma) characteristically expresses CD30 and HLA-DR. PTCL-NOS (peripheral T-cell lymphoma unspecified) still lacks a relatively specific phenotype and is prone to loss of basic lineage markers CD3, CD5, and CD7. The determination of T-CUS can be verified by the overall assessment of the bone marrow and a certain period of follow-up. The clustering results showed that the expression of 8 specific markers was significantly different among the 5 groups, suggesting that a combination of related markers can be analyzed in the identification of PTCLs subtypes. The study explores the advantages of TRBC1 combined with CD45RA/CD45RO in detecting T cell clonality, which can efficiently and sensitively analyze multiple target T cell populations at the same time. The sensitivity of PB to replace BM to monitor the tumor burden or MRD (minimal residual disease) of PTCLs is as high as 85.71%, which can relieve the huge pressure of clinical sampling and improve patient compliance. CD7, CD38, and Ki-67 are prognostic indicators for AITL. CD3 and CD8 on PTCL-NOS, and CD56 and HLA-DR on ENKTL-N have prognostic role. This study supports and validates the current classification of PTCL subtypes and establishes an immunophenotypic profile that can be used for precise diagnosis. The important clinical value of PTCLs immunophenotype in routine classification diagnosis, clonality confirmation, prognosis prediction, and treatment target selection was emphasized.
IFITM protein regulation and functions: Far beyond the fight against viruses
Authors: Friedlová Nela , Zavadil Kokáš Filip , Hupp Ted R. , Vojtěšek Bořivoj , Nekulová Marta
Published: November 2022

Interferons (IFNs) are important cytokines that regulate immune responses through the activation of hundreds of genes, including interferon-induced transmembrane proteins (IFITMs). This evolutionarily conserved protein family includes five functionally active homologs in humans. Despite the high sequence homology, IFITMs vary in expression, subcellular localization and function. The initially described adhesive and antiproliferative or pro-oncogenic functions of IFITM proteins were diluted by the discovery of their antiviral properties. The large set of viruses that is inhibited by these proteins is constantly expanding, as are the possible mechanisms of action. In addition to their beneficial antiviral effects, IFITM proteins are often upregulated in a broad spectrum of cancers. IFITM proteins have been linked to most hallmarks of cancer, including tumor cell proliferation, therapeutic resistance, angiogenesis, invasion, and metastasis. Recent studies have described the involvement of IFITM proteins in antitumor immunity. This review summarizes various levels of IFITM protein regulation and the physiological and pathological functions of these proteins, with an emphasis on tumorigenesis and antitumor immunity.
Over-expression of CRTH2 indicates eosinophilic inflammation and poor prognosis in recurrent nasal polyps
Authors: Chen Wenhui , He Shaojuan , Xie Xinyu , Yang Xiaorong , Duan Chen , Ye Ping , Li Xuezhong , Lawrence Monica G. , Borish Larry , Feng Xin
Published: November 2022

Background

Chronic rhinosinusitis with nasal polyps (CRSwNP) is often characterized by recurrent nasal polyp (NP) growth following surgical removal, but the mechanisms are still not clear. This study aimed to investigate the expression of chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) receptor on NP and the role it plays in eosinophil inflammation and polyp recurrence.

Methods

Forty-one CRSwNPs patients and seventeen controls were enrolled in this study. mRNA was extracted from nasal tissues and evaluated for expression of CRTH2. Immunofluorescence staining was performed to confirm the distribution and expression of CRTH2 protein. CRTH2 expression on peripheral blood eosinophils was quantified by flow cytometry. The eosinophil count and clinical implications were also evaluated and their correlations with CRTH2 expression were analyzed.

Results

Nasal polyps displayed increased expression of CRTH2 in mRNA level compared with control samples, with the highest expression observed in recurrent NP. Immunofluorescence confirmed over-expression of CRTH2 in recurrent NP and this was independent of the concurrent presence of asthma. CRTH2 expression was positively correlated with tissue eosinophil number (Spearman’s ρ=0.69,P<0.001) and the postoperative sino-nasal outcome test-22 (SNOT-22) score (Spearman’s ρ=0.67,P<0.001). Receiver operating characteristic (ROC) curves revealed CRTH2 was more predictive for NP recurrence compared to either eosinophil number and concomitant asthma, with an area under the ROC curve of 0.9107.

Conclusion

The over-expression of CRTH2 in recurrent nasal polyps correlates with greater eosinophilic inflammation and poor prognosis which is independent of concomitant asthma.
αDβ2 as a novel target of experimental polymicrobial sepsis
Authors: Koutsogiannaki Sophia , Hou Lifei , Okuno Toshiaki , Shibamura-Fujiogi Miho , Luo Hongbo R. , Yuki Koichi
Published: November 2022

Since sepsis was defined three decades ago, it has been a target of intensive study. However, there is no specific sepsis treatment available, with its high mortality and morbidity. αDβ2 (CD11d/CD18) is one of the four β2 integrin members. Its role in sepsis has been limitedly studied. Using an experimental polymicrobial sepsis model, we found that the deficiency of αDβ2 was associated with less lung injury and better outcome, which was in sharp contrast to other β2 integrin member αLβ2 (CD11a/CD18), and αMβ2 (CD11b/CD18). This phenotype was supported by a reduction of bacterial loads in αDβ2 knockout mice. Further analysis showed that the deficiency of αDβ2 led to a reduction of neutrophil cell death as well as an increase in neutrophil phagocytosis in both murine and human systems. Our data showed a unique role of αDβ2 among the β2 integrin members, which would serve as a potential target to improve the outcome of sepsis.
HLA-associated outcomes in peanut oral immunotherapy trials identify mechanistic and clinical determinants of therapeutic success
Authors: Kanchan Kanika , Shankar Gautam , Huffaker Michelle F. , Bahnson Henry T. , Chinthrajah R Sharon , Sanda Srinath , Manohar Monali , Ling Hua , Paschall Justin E. , Toit George Du , Ruczinski Ingo , Togias Alkis , Lack Gideon , Nadeau Kari C. , Jones Stacie M. , Nepom Gerald T. , Mathias Rasika A.
Published: November 2022

Rationale

Previous studies identified an interaction between HLA and oral peanut exposure. HLA-DQA1*01:02 had a protective role with the induction of Ara h 2 epitope-specific IgG4 associated with peanut consumption during the LEAP clinical trial for prevention of peanut allergy, while it was a risk allele for peanut allergy in the peanut avoidance group. We have now evaluated this gene-environment interaction in two subsequent peanut oral immunotherapy (OIT) trials - IMPACT and POISED - to better understand the potential for the HLA-DQA1*01:02 allele as an indicator of higher likelihood of desensitization, sustained unresponsiveness, and peanut allergy remission.

Methods

We determined HLA-DQA1*01:02 carrier status using genome sequencing from POISED (N=118, age: 7-55yr) and IMPACT (N=126, age: 12-<48mo). We tested for association with remission, sustained unresponsiveness (SU), and desensitization in the OIT groups, as well as peanut component specific IgG4 (psIgG4) using generalized linear models and adjusting for relevant covariates and ancestry.

Results

While not quite statistically significant, a higher proportion of HLA-DQA1*01:02 carriers receiving OIT in IMPACT were desensitized (93%) compared to non-carriers (78%); odds ratio (OR)=5.74 (p=0.06). In this sample we also observed that a higher proportion of carriers achieved remission (35%) compared to non-carriers (22%); OR=1.26 (p=0.80). In POISED, carriers more frequently attained continued desensitization (80% versus 61% among non-carriers; OR=1.28, p=0.86) and achieved SU (52% versus 31%; OR=2.32, p=0.19). psIgG4 associations with HLA-DQA1*01:02 in the OIT arm of IMPACT which included younger study subjects recapitulated patterns noted in LEAP, but no associations of note were observed in the older POISED study subjects.

Conclusions

Findings across three clinical trials show a pattern of a gene environment interaction between HLA and oral peanut exposure. Age, and prior sensitization contribute additional determinants of outcomes, consistent with a mechanism of restricted antigen recognition fundamental to driving protective immune responses to OIT.
Honeybees are buffered against undernourishment during larval stages
Authors: Schilcher Felix , Hilsmann Lioba , Ankenbrand Markus J. , Krischke Markus , Mueller Martin J. , Steffan-Dewenter Ingolf , Scheiner Ricarda
Published: November 2022

The negative impact of juvenile undernourishment on adult behavior has been well reported for vertebrates, but relatively little is known about invertebrates. In honeybees, nutrition has long been known to affect task performance and timing of behavioral transitions. Whether and how a dietary restriction during larval development affects the task performance of adult honeybees is largely unknown. We raised honeybees in-vitro, varying the amount of a standardized diet (150 µl, 160 µl, 180 µl in total). Emerging adults were marked and inserted into established colonies. Behavioral performance of nurse bees and foragers was investigated and physiological factors known to be involved in the regulation of social organization were quantified. Surprisingly, adult honeybees raised under different feeding regimes did not differ in any of the behaviors observed. No differences were observed in physiological parameters apart from weight. Honeybees were lighter when undernourished (150 µl), while they were heavier under the overfed treatment (180 µl) compared to the control group raised under a normal diet (160 µl). These data suggest that dietary restrictions during larval development do not affect task performance or physiology in this social insect despite producing clear effects on adult weight. We speculate that possible effects of larval undernourishment might be compensated during the early period of adult life.
Seasonal variability of eddy kinetic energy in the north Indian Ocean
Authors: Sun Chunjian , Zhang Anmin , Jin Baogang , Wang Xidong , Zhang Xiaoshuang , Zhang Lianxin
Published: November 2022

The seasonality of eddy kinetic energy (EKE) is analyzed in the north Indian Ocean by adopting high-resolution ocean reanalysis data. Significant eddy energy can be mainly spotted in six regions, including the Somali Current (SC) region, the Gulf of Aden, the Laccadive Sea, the east of Sri Lanka, the East Indian Coastal Current (EICC) region, and the northwest of Sumatra. As the most energetic region, the EKE averaged above 200 m could exceed 0.15 m2·s-2 in the SC region, whereas the mean EKE above 200 m is less than 0.04 m2·s-2 in the other regions. The barotropic and baroclinic instabilities are vital to eddy energy, and the contribution of each term in the barotropic/baroclinic equations varies with season and region. In the SC region and EICC region, EKE is primarily generated by barotropic conversion due to the sharp velocity shear caused by the strong SC during the summer monsoon and the EICC from March to June. For the other regions, the leading source of EKE is the eddy potential energy (EPE), which is extracted from available potential energy of mean flow via baroclinic conversion, and then the EPE is converted into EKE through vertical density flux. Once generated, EKE will be redistributed by pressure work and advection via eddy energy flux, which varies in sync with the monthly variation of total EKE, transporting EKE to the adjacent region or deeper layer. From the vertical aspect, eddy energy conversions are more prominent above 200 m. The maximal EKE and barotropic conversion mostly occur at the surface, whereas the EPE and baroclinic conversion may have two peaks, which lie at the surface and in the thermocline. Using the satellite altimeter data and wind data, we further investigate the impact of geostrophic eddy wind work, which reveals a slightly dampening effect to EKE in the north Indian Ocean.
Design of human immunodeficiency virus-1 neutralizing peptides targeting CD4-binding site: An integrative computational biologics approach
Authors: Vivekanandan Sandhya , Vetrivel Umashankar , Hanna Luke Elizabeth
Published: November 2022

Peptide therapeutics have recently gained momentum in antiviral therapy due to their increased potency and cost-effectiveness. Interaction of the HIV-1 envelope gp120 with the host CD4 receptor is a critical step for viral entry, and therefore the CD4-binding site (CD4bs) of gp120 is a potential hotspot for blocking HIV-1 infection. The present study aimed to design short peptides from well-characterized CD4bs targeting broadly neutralizing antibodies (bNAbs), which could be utilized as bNAb mimetics for viral neutralization. Co-crystallized structures of HIV-1 gp120 in complex with CD4bs-directed bNAbs were used to derive hexameric peptides using the Rosetta Peptiderive protocol. Based on empirical insights into co-crystallized structures, peptides derived from the heavy chain alone were considered. The peptides were docked with both HIV-1 subtype B and C gp120, and the stability of the peptide–antigen complexes was validated using extensive Molecular Dynamics (MD) simulations. Two peptides identified in the study demonstrated stable intermolecular interactions with SER365, GLY366, and GLY367 of the PHE43 cavity in the CD4 binding pocket, and with ASP368 of HIV-1 gp120, thereby mimicking the natural interaction between ASP368gp120 and ARG59CD4–RECEPTOR. Furthermore, the peptides featured favorable physico-chemical properties for virus neutralization suggesting that these peptides may be highly promising bNAb mimetic candidates that may be taken up for experimental validation.
Five years follow up of patient receiving prolonged mechanical ventilation: Data for a single center in Taiwan
Authors: Huang Chienhsiu
Published: November 2022

Background

The National Association for Medical Direction of Respiratory Care recommended tracking 1-year survival rates (the most relevant outcome) in patients treated with prolonged mechanical ventilation. However, patients treated with prolonged mechanical ventilation had higher mortality rates within the first 2 years after weaning. More knowledge regarding long-term mortality would help patients, families, and clinicians choose appropriate interventions and make end-of-life decisions. In this investigation, we attempted to determine the rates of long-term mortality for all patients treated with prolonged mechanical ventilation over a period of 10 years.

Objective

The purpose of this investigation was to enhance the overall survival outcomes for patients receiving prolonged mechanical ventilation by identifying the factors affecting the 5-year mortality rates for these patients.

Design

Retrospective observational study.

Materials and methods

In this retrospective study, we explored the influential factors related to the overall survival outcomes of all patients treated with prolonged mechanical ventilation. We enrolled every individual admitted to the weaning unit between January 1, 2012, and December 31, 2016. The length of survival for each patient was estimated from admission to the weaning unit until death or December 31, 2021, whichever came first. We analyzed the data to investigate the survival time, mortality rates, and survival curves in these patients.

Results

Long-term follow-up information was gathered for 296 patients who received prolonged mechanical ventilation. There was better mean survival times in patients treated with prolonged mechanical ventilation with the following characteristics (in order): no comorbidities, tracheostomies, and intracranial hemorrhage. Successful weaning, receipt of tracheostomy, an age less than 75 years, and no comorbidities were associated with better long-term overall survival outcomes.

Conclusion

Prolonged mechanical ventilation patients had abysmal overall survival outcomes. Even though prolonged mechanical ventilation patients’ long-term survival outcomes are tragic, medical professionals should never give up on the dream of enhancing long-term outcomes.
Pre-operative anemia was associated with all-cause mortality in patients with vertebral fracture who underwent percutaneous vertebroplasty
Authors: Wu Yun-Che , Lin Yu-Hsien , Lin Yu-Tsung , Wang Wen-Chien , Chen Kun-Hui , Pan Chien-Chou , Wang Jun-Sing , Lee Cheng-Hung
Published: November 2022

Purpose

We investigated the association between pre-operative anemia and long-term all-cause mortality in patients with vertebral fracture who underwent a vertebroplasty.

Materials and methods

We retrospectively selected patients who were admitted for vertebroplasty for vertebral compression fracture between 2013 and 2020. Patients who had pathologic fractures or had no assessment of bone mineral density were excluded. Relevant information was collected from electronic medical records. Patients’ survival status was confirmed at the end of March 2021. Cox-proportional hazard models were conducted to examine the effects of anemia (<12 g/dL vs. ≥12 g/dL) and pre-operative hemoglobin levels (as a continuous variable) on all-cause mortality with multivariate adjustments.

Results

A total of 167 patients were analyzed (mean age 75.8 ± 9.3 years, male 25.7%). After a median follow-up duration of 2.1 years, pre-operative anemia (hemoglobin <12 g/dL vs. ≥12 g/dL) was independently associated with a higher risk of all-cause mortality (hazard ratio 2.762, 95% CI 1.184 to 6.442, p = 0.019). An increase in pre-operative hemoglobin was associated with a lower risk of all-cause mortality after multivariate adjustment (hazard ratio 0.775, 95% CI 0.606 to 0.991, p = 0.042).

Conclusion

Pre-operative anemia (<12 g/dL) was independently associated with survival outcome among patients with vertebral compression fractures who underwent vertebroplasty. Our findings highlight anemia as a risk factor of long-term mortality in this elderly surgical population.
Treatment of cutaneous vasculitis
Authors: Micheletti Robert G.
Published: November 2022

Cutaneous vasculitis encompasses a spectrum of disease states, with varied morphology, severity, and potential for systemic involvement. Even vasculitis which is skin-limited can have a significant quality-of-life impact, necessitating treatment. This manuscript summarizes the available evidence for management of various types of skin-limited vasculitis and provides a proposed therapeutic ladder based on published studies and expert opinion.
Effects of supplementation of sodium acetate on rumen fermentation and microbiota in postpartum dairy cows
Authors: Cheng Zhiqiang , Meng Zitong , Tan Dejin , Datsomor Osmond , Zhan Kang , Lin Miao , Zhao Guoqi
Published: November 2022

The primary product of rumen fermentation is acetic acid, and its sodium salt is an excellent energy source for post-partum cows to manage negative energy balance (NEB). However, it is unknown how adding sodium acetate (NAc) may affect the rumen bacterial population of post-partum cows. Using the identical nutritional total mixed ration (TMR), this research sought to characterize the impact of NAc supplementation on rumen fermentation and the composition of bacterial communities in post-partum cows. After calving, 24 cows were randomly assigned to two groups of 12 cows each: a control group (CON) and a NAc group (ACE). All cows were fed the same basal TMR with 468 g/d NaCl added to the TMR for the CON group and 656 g/d NAc added to the TMR for the ACE group for 21 days after calving. Ruminal fluid was collected before morning feeding on the last day of the feeding period and analyzed for rumen bacterial community composition by 16S rRNA gene sequencing. Under the identical TMR diet conditions, NAc supplementation did not change rumen pH but increased ammonia nitrogen (NH3-N) levels and microbial crude protein (MCP) concentrations. The administration of NAc to the feed upregulated rumen concentrations of total volatile fatty acids (TVFA), acetic, propionic, isovaleric and isobutyric acids without affecting the molar ratio of VFAs. In the two experimental groups, the Bacteroidota, Firmicutes, Patescibacteria and Proteobacteria were the dominant rumen phylum, and Prevotella was the dominant rumen genus. The administration of NAc had no significant influence on the α-diversity of the rumen bacterial community but upregulated the relative abundance of Prevotella and downregulated the relative abundance of RF39 and Clostridia_UCG_014. In conclusion, the NAc supplementation in the post-peripartum period altered rumen flora structure and thus improved rumen fermentation in dairy cows. Our findings provide a reference for the addition of sodium acetate to alleviate NEB in cows during the late perinatal period.
Antibiotic resistance and host immune system-induced metal bactericidal control are key factors for microbial persistence in the developing human preterm infant gut microbiome
Authors: Peters Samantha L. , Morowitz Michael J. , Hettich Robert L.
Published: November 2022

The human gut microbiome, which develops and stabilizes during the early stages of infant life, plays an essential role in host health through the production of metabolic resources and the stimulation and training of the immune system. To study colonization and community functional dynamics of the microbiota based on responses to host immune processes during the normal and dysbiotic establishment of the gut, metaproteomics was conducted on 91 fecal samples collected over the first 90 days of life from 17 hospitalized premature infants. Microbial responses to antibiotic administration and host-imposed metal bactericidal control correlated with community assembly and resiliency of microbes in the developing preterm gut. Specifically, proteins related to antibiotic resistance and metal homeostasis mechanisms were predominant in persisting members in the infant gut environment over the first several weeks of life. Overall, this metaproteomics study provides a unique approach to examine the temporal expansion and resilience of microbial colonization, as it allows simultaneous examination of both host and microbial metabolic activities. Understanding the interplay between host and microbes may elucidate the microbiome’s potential immunomodulatory roles relevant to necrotizing enterocolitis and other dysbiotic conditions in preterm infants.
Spatio-temporal changes in endosymbiont diversity and composition in the African cassava whitefly, Bemisia tabaci SSA1
Authors: El Hamss Hajar , Maruthi M. N. , Ally Hadija M. , Omongo Christopher A. , Wang Hua-Ling , van Brunschot Sharon , Colvin John , Delatte Hélène
Published: November 2022

Sap-sucking insects, including whiteflies, are amongst the most devastating and widely distributed organisms on the planet. They are often highly invasive and endosymbiont communities within these insects help them adapt to new or changing environments. Bemisia tabaci (Gennadius; Hemiptera: Aleyrodidae) whitefly species are vectors of more than 500 known plant-viruses and harbour highly diverse endosymbionts communities. To date, however, whitefly–endosymbiont interactions, community structure and their spatio-temporal changes are still poorly understood. In this study, we investigated the spatio-temporal changes in the composition and diversity of bacterial endosymbionts in the agricultural crop pest whitefly species, Bemisia tabaci sub-Saharan Africa 1-subgroup 1 and 2 (SSA1-SG1 and SSA1-SG2). 16S rRNA amplicon sequencing analysis was carried out to characterise endosymbiont compositionsin field-collected SSA1 (SSA1-SG1 and SSA1-SG2) populations infesting cassava in Uganda in 1997 and 2017. We detected Portiera, Arsenophonus, Wolbachia, Hamiltonella and Hemipteriphilus, with Arsenophonus and Wolbachia infections being predominant. Hemipteriphilus and Hamiltonella frequencies were very low and were detected in seven and two samples, respectively. Bacterial diversity based on three independent parameters including Simpson index, number of haplotypes and Bray–Curtis dissimilarity matrix was significantly higher in 1997 than in 2017. This period also coincided with the advent of super-abundant cassava-whitefly populations on cassava crops in Uganda. We discuss how endosymbionts may influence the biology and behaviour of whiteflies leading to population explosions.
Friends in need: How chaperonins recognize and remodel proteins that require folding assistance
Authors: Stan George , Lorimer George H. , Thirumalai D.
Published: November 2022

Chaperonins are biological nanomachines that help newly translated proteins to fold by rescuing them from kinetically trapped misfolded states. Protein folding assistance by the chaperonin machinery is obligatory in vivo for a subset of proteins in the bacterial proteome. Chaperonins are large oligomeric complexes, with unusual seven fold symmetry (group I) or eight/nine fold symmetry (group II), that form double-ring constructs, enclosing a central cavity that serves as the folding chamber. Dramatic large-scale conformational changes, that take place during ATP-driven cycles, allow chaperonins to bind misfolded proteins, encapsulate them into the expanded cavity and release them back into the cellular environment, regardless of whether they are folded or not. The theory associated with the iterative annealing mechanism, which incorporated the conformational free energy landscape description of protein folding, quantitatively explains most, if not all, the available data. Misfolded conformations are associated with low energy minima in a rugged energy landscape. Random disruptions of these low energy conformations result in higher free energy, less folded, conformations that can stochastically partition into the native state. Two distinct mechanisms of annealing action have been described. Group I chaperonins (GroEL homologues in eubacteria and endosymbiotic organelles), recognize a large number of misfolded proteins non-specifically and operate through highly coordinated cooperative motions. By contrast, the less well understood group II chaperonins (CCT in Eukarya and thermosome/TF55 in Archaea), assist a selected set of substrate proteins. Sequential conformational changes within a CCT ring are observed, perhaps promoting domain-by-domain substrate folding. Chaperonins are implicated in bacterial infection, autoimmune disease, as well as protein aggregation and degradation diseases. Understanding the chaperonin mechanism and the specific proteins they rescue during the cell cycle is important not only for the fundamental aspect of protein folding in the cellular environment, but also for effective therapeutic strategies.
Environmental enrichment improves declined cognition induced by prenatal inflammatory exposure in aged CD-1 mice: Role of NGPF2 and PSD-95
Authors: Ni Ming-Zhu , Zhang Yue-Ming , Li Yun , Wu Qi-Tao , Zhang Zhe-Zhe , Chen Jing , Luo Bao-Ling , Li Xue-Wei , Chen Gui-Hai
Published: November 2022

Introduction

Research suggests that prenatal inflammatory exposure could accelerate age-related cognitive decline that may be resulted from neuroinflammation and synaptic dysfunction during aging. Environmental enrichment (EE) may mitigate the cognitive and synaptic deficits. Neurite growth-promoting factor 2 (NGPF2) and postsynaptic density protein 95 (PSD-95) play critical roles in neuroinflammation and synaptic function, respectively.

Methods

We examined whether this adversity and EE exposure can cause alterations in Ngpf2 and Psd-95 expression. In this study, CD-1 mice received intraperitoneal injection of lipopolysaccharide (50 μg/kg) or normal saline from gestational days 15–17. After weaning, half of the male offspring under each treatment were exposed to EE. The Morris water maze was used to assess spatial learning and memory at 3 and 15 months of age, whereas quantitative real-time polymerase chain reaction and Western blotting were used to measure hippocampal mRNA and protein levels of NGPF2 and PSD-95, respectively. Meanwhile, serum levels of IL-6, IL-1β, and TNF-α were determined by enzyme-linked immunosorbent assay.

Results

The results showed that aged mice exhibited poor spatial learning and memory ability, elevated NGPF2 mRNA and protein levels, and decreased PSD-95 mRNA and protein levels relative to their young counterparts during natural aging. Embryonic inflammatory exposure accelerated age-related changes in spatial cognition, and in Ngpf2 and Psd-95 expression. Additionally, the levels of Ngpf2 and Psd-95 products were significantly positively and negatively correlated with cognitive dysfunction, respectively, particularly in prenatal inflammation-exposed aged mice. Changes in serum levels of IL-6, IL-1β, and TNF-α reflective of systemic inflammation and their correlation with cognitive decline during accelerated aging were similar to those of hippocampal NGPF2. EE exposure could partially restore the accelerated decline in age-related cognitive function and in Psd-95 expression, especially in aged mice.

Discussion

Overall, the aggravated cognitive disabilities in aged mice may be related to the alterations in Ngpf2 and Psd-95 expression and in systemic state of inflammation due to prenatal inflammatory exposure, and long-term EE exposure may ameliorate this cognitive impairment by upregulating Psd-95 expression.
Synthesis methods and applications of palladium nanoparticles: A review
Authors: Joudeh Nadeem , Saragliadis Athanasios , Koster Gerbrand , Mikheenko Pavlo , Linke Dirk
Published: November 2022

Palladium (Pd) is a key component of many catalysts. Nanoparticles (NPs) offer a larger surface area than bulk materials, and with Pd cost increasing 5-fold in the last 10 years, Pd NPs are in increasing demand. Due to novel or enhanced physicochemical properties that Pd NPs exhibit at the nanoscale, Pd NPs have a wide range of applications not only in chemical catalysis, but also for example in hydrogen sensing and storage, and in medicine in photothermal, antibacterial, and anticancer therapies. Pd NPs, on the industrial scale, are currently synthesized using various chemical and physical methods. The physical methods require energy-intensive processes that include maintaining high temperatures and/or pressure. The chemical methods usually involve harmful solvents, hazardous reducing or stabilizing agents, or produce toxic pollutants and by-products. Lately, more environmentally friendly approaches for the synthesis of Pd NPs have emerged. These new approaches are based on the use of the reducing ability of phytochemicals and other biomolecules to chemically reduce Pd ions and form NPs. In this review, we describe the common physical and chemical methods used for the synthesis of Pd NPs and compare them to the plant- and bacteria-mediated biogenic synthesis methods. As size and shape determine many of the unique properties of Pd NPs on the nanoscale, special emphasis is given to the control of these parameters, clarifying how they impact current and future applications of this exciting nanomaterial.
Design and torque control base on neural network PID of a variable stiffness joint for rehabilitation robot
Authors: Hu Bingshan , Mao Binghao , Lu Sheng , Yu Hongliu
Published: November 2022

Variable stiffness joints have been gradually applied in rehabilitation robots because of their intrinsic compliance and greater ability to adjust mechanical stiffness. This paper designs a variable stiffness joint for upper limb rehabilitation training. The joint adopts the variable stiffness principle based special curved surface. The trapezoidal lead screw in the variable stiffness module has a self-locking function, and the stiffness can be maintained without the continuous output torque of the motor. In the aspect of control, back propagation (BP) neural network PID control strategy is used to control the torque of variable stiffness joint. Experiments show that this control method can effectively improve the torque control performance of variable stiffness joints in the case of low stiffness, and the isotonic centripetal resistance training can be realized by using the joints and control methods designed in this paper.
Barriers to exercise and the role of general practitioner: A cross-sectional survey among people with multiple sclerosis
Authors: Correale Luca , Martinis Luca , Tavazzi Eleonora , Pedullà Ludovico , Mallucci Giulia , Brichetto Giampaolo , Bove Marco , Ponzio Michela , Borrelli Paola , Monti Maria Cristina , Bergamaschi Roberto , Montomoli Cristina
Published: November 2022

Introduction

Regular exercise is strongly recommended for people with MS (pwMS), but recent studies still describe them as sedentary and insufficiently active. The purpose of this study is to identify the major barriers that prevent pwMS from exercising and underline the importance of the general practitioner (GP) in promoting an active lifestyle.

Materials and methods

We performed a multicenter cross-sectional study using a self-administered questionnaire among pwMS. Data about demographics, the disease, current exercise practice, barriers, previous GP's advice to practice, and motivation were collected.

Results

A total of 741 pwMS (age 55.6 ± 12.5 years, 66% females) completed the survey. Most responders (75.3%) did not practice any exercise. Fatigue was the most limiting factor to attending and/or starting an exercise program, followed by travel and/or moving issues, and the lack of time. Only 25.5% of participants received GP's advice to practice exercise, but 48.6% of them attended an exercise program. A greater likelihood of practice was evidenced for people that received the GP's advice than those who had not received it (OR 2.96; p < 0.001). Finally, among those who did not practice exercise but received advice from GPs, 69 out of 99 (69.7%) were motivated to start an exercise program.

Conclusion

Fatigue and physical issues are the main barriers to exercise for pwMS, but also other factors not related to the disease seem to be relevant, like travel issues and lack of time. Although few participants received advice to exercise from their general practitioner, his role proved effective in encouraging the practice.
Alteration of brain nuclei in obese children with and without Prader-Willi syndrome
Authors: Wu Ning , Yu Huan , Xu Mingze
Published: November 2022

Introduction: Prader-Willi syndrome (PWS) is a multisystem genetic imprinting disorder mainly characterized by hyperphagia and childhood obesity. Extensive structural alterations are expected in PWS patients, and their influence on brain nuclei should be early and profound. To date, few studies have investigated brain nuclei in children with PWS, although functional and structural alterations of the cortex have been reported widely.

Methods: In the current study, we used T1-weighted magnetic resonance imaging to investigate alterations in brain nuclei by three automated analysis methods: shape analysis to evaluate the shape of 14 cerebral nuclei (bilateral thalamus, caudate, putamen, globus pallidus, hippocampus, amygdala, and nucleus accumbens), automated segmentation methods integrated in Freesurfer 7.2.0 to investigate the volume of hypothalamic subregions, and region of interest-based analysis to investigate the volume of deep cerebellar nuclei (DCN). Twelve age- and sex-matched children with PWS, 18 obese children without PWS (OB) and 18 healthy controls participated in this study.

Results: Compared with control and OB individuals, the PWS group exhibited significant atrophy in the bilateral thalamus, pallidum, hippocampus, amygdala, nucleus accumbens, right caudate, bilateral hypothalamus (left anterior-inferior, bilateral posterior, and bilateral tubular inferior subunits) and bilateral DCN (dentate, interposed, and fastigial nuclei), whereas no significant difference was found between the OB and control groups.

Discussion: Based on our evidence, we suggested that alterations in brain nuclei influenced by imprinted genes were associated with clinical manifestations of PWS, such as eating disorders, cognitive disability and endocrine abnormalities, which were distinct from the neural mechanisms of obese children.
Transcriptomic analysis identifies shared biological foundations between ischemic stroke and Alzheimer’s disease
Authors: Liu Wenhao , Wan Mengyao , Shi Yinchao , Yang Xin-Zhuang
Published: November 2022

Aim

Alzheimer’s disease (AD) and ischemic stroke (IS), two major neurological diseases, are suggested to be associated in clinical and pathophysiological levels. Previous studies have provided some insights into the possible genetic mechanisms behind the correlation between AD and IS, but this issue is still not clear. We implemented transcriptomic analysis to detect common hub genes and pathways to help promote the understanding of this issue.

Materials and methods

Four gene expression profiling datasets (GSE16561, GSE58294, GSE63060, and GSE63061) of peripheral whole blood, which contain 108 IS samples, 284 AD samples, and 285 matched controls, were employed to detect differentially expressed genes (DEGs) for AD and IS, which were further analyzed for shared biological pathways, candidate drugs, and transcription factors. Protein-protein interaction (PPI) network and drug-target interaction analysis were applied to identify hub genes and drug targets, respectively. Result verification was done with other independent datasets (GSE37587, GSE46480, and GSE140829). The difference in proportions of various immune cells in the peripheral blood of AD and IS patients were evaluated using CIBERSORT.

Results

We identified 74 DEGs and 18 biological processes with statistical significance shared by AD and IS, 9 of which were immune-related pathways. Five hub genes scored high in the topological analysis of the PPI network, and we also found eight drug target genes and candidate drugs which were associated with AD and IS. As for immunological changes, an increase in the proportion of M0 macrophages was found in the peripheral circulation of both AD and IS patients, and SOD1 expression was significantly correlated with this change.

Conclusion

Collectively, the common DEGs and shared pathways found in this study suggest a potential shared etiology between AD and IS, behind which immune system, particularly the M0 macrophage elevation, might have important roles. While, the shared hub genes, potential therapeutic gene targets and drugs reported in this study provide promising treatment strategies for AD and IS.
Perspective on “code qualifying” new graphite grades for use in advanced nuclear reactors*
Authors: Campbell Anne A.
Published: November 2022

The American Society of Mechanical Engineers (ASME) publishes the Boiler and Pressure Vessel (BPV) Code, which include guidance for the safe development, construction, and operation of boilers and pressure vessels. ASME BPV Code Section III “Rules for Construction of Nuclear Facility Components” Division 5 focuses on “High Temperature Reactors”. Subsection HH, subpart A lists the different materials properties that are to be measured and how those properties change due to different environmental conditions (oxidation and irradiation damage) for a graphite to be accepted for use in a high temperature reactor core (i.e., “Code Qualified”). Currently there are no nuclear graphite grades that are “Code Qualified” (i.e., a reactor designer can select a graphite grade and build their reactor without any additional testing), which is due in part to development of new graphite grades in the last 20 years and the lack of comprehensive programs needed to produce the data for the code cases. This perspective is going to discuss the requirements, as called out in the ASME BPV Code, that are necessary to “code qualify” a nuclear graphite grade but will primarily focus on the practical and technical challenges associated with irradiation-induced property changes and how to address these to assist with getting graphite ready for use in advanced nuclear reactors. These same technical challenges can be expected to arise for other materials being developed for advanced reactor concepts.
Microbial treatment of alcoholic liver disease: A systematic review and meta-analysis
Authors: Wang Qinjian , Shi Jiangmin , Zhao Min , Ruan Gaoyi , Dai Zebin , Xue Yilang , Shi Dibang , Xu Changlong , Yu Ouyue , Wang Fangyan , Xue Zhanxiong
Published: November 2022

Background and aims

Alcoholic liver disease (ALD) is characterized by impaired liver function due to chronic alcohol consumption, even fatal in severe cases. We performed a meta-analysis to determine whether microbial agents have therapeutic potential for ALD and elucidate the underlying mechanisms.

Methods and results

Forty-one studies were eligible for this meta-analysis after searching the PubMed, Cochrane, and Embase databases. The combined analysis showed that microbial therapy significantly decreased hepatic enzymatic parameters, including alanine transaminase [standardized mean difference (SMD): –2.70, 95% confidence interval (CI): –3.33 to –2.07], aspartate aminotransferase (SMD: –3.37, 95% CI: –4.25 to –2.49), γ-glutamyl transpeptidase (SMD: -2.07, 95% CI: –3.01 to –1.12), and alkaline phosphatase (SMD: –2.12, 95% CI: –3.32 to –0.92). Microbial agents endotoxin to enter the portal circulation and increasing reduced total cholesterol (SMD = -2.75, 95%CI -4.03 to -1.46) and triglycerides (SMD = –2.64, 95% CI: –3.22 to –2.06). Microbial agents increased amounts of the beneficial flora Lactobacillus (SMD: 4.40, 95% CI: 0.97–7.84) and Bifidobacteria (SMD: 3.84, 95% CI: 0.22–7.45), Bacteroidetes (SMD: 2.51, 95% CI: 0.29–4.72) and decreased harmful Proteobacteria (SMD: –4.18, 95% CI: –6.60 to –1.77), protecting the integrity of the intestinal epithelium and relieving endotoxin (SMD: –2.70, 95% CI: -3.52 to –2.17) into the portal vein, thereby reducing the production of inflammatory factors such as tumor necrosis factor-α (SMD: –3.35, 95% CI: –4.31 to –2.38), interleukin-6 (SMD: –4.28, 95% CI: –6.13 to –2.43), and interleukin-1β (SMD: –4.28, 95% CI: –6.37 to –2.19). Oxidative stress was also relieved, as evidenced by decreased malondialdehyde levels (SMD: –4.70, 95% CI: –6.21 to –3.20). Superoxide dismutase (SMD: 2.65, 95% CI: 2.16–3.15) and glutathione levels (SMD: 3.80, 95% CI: 0.95–6.66) were elevated.

Conclusion

Microbial agents can reverse dysbiosis in ALD, thus significantly interfering with lipid metabolism, relieving inflammatory response and inhibiting oxidative stress to improve liver function.