bluuebunny/crossref_metadata_2025 huggingface dataset:
Biological Control Efficacy and Action Mechanism of Klebsiella pneumoniae JCK-2201 Producing Meso-2,3-Butanediol Against Tomato Bacterial Wilt
Authors: Kim Bora , Park Ae Ran , Song Chan Woo , Song Hyohak , Kim Jin-Cheol
Published: July 2022

Bacterial wilt caused byRalstonia solanacearumis a fatal disease that affects the production of tomatoes and many other crops worldwide. As an effective strategy to manage bacterial wilt, biological control agents using plant growth-promoting rhizobacteria (PGPR) are being developed. In this study, we screened 2,3-butanediol (BDO)-producing PGPR to control tomato bacterial wilt and investigated the action mechanism of the disease control agent. Of the 943 strains isolated from soil,Klebsiella pneumoniaestrain JCK-2201 produced the highest concentration of 2,3-BDO. The culture broth ofK. pneumoniaeJCK-2201 did not show any direct activity onR. solanacearum in vitro, but a 100-fold dilution effectively controlled tomato bacterial wilt with a control value of 77%in vivo. Fermentation utilizingK. pneumoniaeJCK-2201 was optimized to produce 48 g/L of meso-2,3-BDO, which is 50% of the sucrose conversion efficiency. In addition, the control efficacy and mechanism of meso-2,3-BDO produced by JCK-2201 in tomato bacterial wilt were determined by comparative analysis withBacillus licheniformisDSM13 producing meso-2,3-BDO andB. licheniformisDSM13ΔalsSthat did not produce 2,3-BDO, as the step of converting pyruvate to α-acetolactate was omitted. Tomato seedlings treated with theK. pneumoniaeJCK-2201 (500-fold dilution) andB. licheniformisDSM13 (100-fold dilution) culture broth produced meso-2,3-BDO that significantly reducedR. solanacearum-induced disease severity with control values of 55% and 63%, respectively. The formulated meso-2,3-BDO 9% soluble concentrate (SL; 1,000-fold dilution) showed 87% control against tomato bacterial wilt in the field condition.Klebsiella pneumoniaeJCK-2201 andB. licheniformisDSM13 treatment induced the expression of plant defense marker genes, such asLePR1,LePR2,LePR5,LePR3, andPI-II, in the salicylic acid and jasmonic acid signaling pathways at 4 days after inoculation. These results show that 2,3-BDO-producing bacteria and 2,3-BDO are potential biological control agents that act through induction of resistance for controlling tomato bacterial wilt.
Root Exudates: Mechanistic Insight of Plant Growth Promoting Rhizobacteria for Sustainable Crop Production
Authors: Upadhyay Sudhir K. , Srivastava Abhishek K. , Rajput Vishnu D. , Chauhan Prabhat K. , Bhojiya Ali Asger , Jain Devendra , Chaubey Gyaneshwer , Dwivedi Padmanabh , Sharma Bechan , Minkina Tatiana
Published: July 2022

The breaking silence between the plant roots and microorganisms in the rhizosphere affects plant growth and physiology by impacting biochemical, molecular, nutritional, and edaphic factors. The components of the root exudates are associated with the microbial population, notably, plant growth-promoting rhizobacteria (PGPR). The information accessible to date demonstrates that PGPR is specific to the plant's roots. However, inadequate information is accessible for developing bio-inoculation/bio-fertilizers for the crop in concern, with satisfactory results at the field level. There is a need to explore the perfect candidate PGPR to meet the need for plant growth and yield. The functions of PGPR and their chemotaxis mobility toward the plant root are triggered by the cluster of genes induced by the components of root exudates. Some reports have indicated the benefit of root exudates in plant growth and productivity, yet a methodical examination of rhizosecretion and its consequences in phytoremediation have not been made. In the light of the afore-mentioned facts, in the present review, the mechanistic insight and recent updates on the specific PGPR recruitment to improve crop production at the field level are methodically addressed.
Salinity-Linked Denitrification Potential in Endorheic Lake Bosten (China) and Its Sensitivity to Climate Change
Authors: Jiang Xingyu , Liu Changqing , Hu Yang , Shao Keqiang , Tang Xiangming , Gao Guang , Qin Boqiang
Published: July 2022

Endorheic lakes in arid regions of Northwest China are generally vulnerable and sensitive to accelerated climate change and extensive human activities. Therefore, a better understanding of the self-purification capacity of ecosystems, such as denitrification, is necessary to effectively protect these water resources. In the present study, we measured unamended and amended denitrification rates of Lake Bosten by adding the ambient and extra nitrate isotopes in slurry incubations. Meanwhile, we investigated the abundances and community structure of nitrous oxide-reducing microorganisms using qPCR and high-throughput sequencing, respectively, in the surface sediments of Lake Bosten to study denitrification potential in endorheic lakes of arid regions as well as the response of those denitrifiers to climatically induced changes in lake environments. Amended denitrification rates increased by one order of magnitude compared to unamended rates in Lake Bosten. The great discrepancy between unamended and amended rates was attributed to low nitrate availability, indicating that Lake Bosten is not operating at maximum capacity of denitrification. Salinity shaped the spatial heterogeneity of denitrification potential through changes in the abundances and species diversity of denitrifiers. Climate change had a positive effect on the water quality of Lake Bosten so far, through increased runoff, decreased salinity, and enhanced denitrification. But the long-term trajectories of water quality are difficult to predict alongside future glacier shrinkage and decreased snow cover.
Metabolites From Trypanosome-Infected Cattle as Sensitive Biomarkers for Animal Trypanosomosis
Authors: Getahun Merid N. , Ngiela John , Makwatta JohnMark O. , Ahuya Peter , Simon Tawich K. , Kamau Samuel K. , Torto Baldwyn , Masiga Daniel
Published: July 2022

Trypanosomes are important global livestock and human pathogens of public health importance. Elucidating the chemical mechanisms of trypanosome-relevant host interactions can enhance the design and development of a novel, next-generation trypanosomosis diagnostics. However, it is unknown how trypanosome infection affects livestock volatile odors. Here, we show that Trypanosoma congolense and Trypanosoma vivax infections induced dihydro-β- ionone and junenol, while abundance of dihydro-α-ionone, phenolics, p-cresol, and 3-propylphenol significantly elevated in cow urine. These biomarkers of trypanosome infection are conserved in cow breath and the urine metabolites of naturally infected cows, regardless of population, diet, or environment differences. Furthermore, treating trypanosome-infected cows reduced the levels of these indicators back to the pre-infection levels. Finally, we demonstrated that the potential of some specific biomarkers of phenolic origin may be used to detect active trypanosome infections, including low-level infections that are not detectable by microscopy. The sensitivity and specificity of biomarkers detection are suited for rapid, robust, and non-invasive trypanosomosis diagnosis under field conditions.
Cultivable Skin Mycobiota of Healthy and Diseased Blind Cave Salamander (Proteus anguinus)
Authors: Zalar Polona , Gubenšek Ana , Gostincar Cene , Kostanjšek Rok , Bizjak-Mali Lilijana , Gunde-Cimerman Nina
Published: July 2022

Proteus anguinus is a neotenic cave salamander, endemic to the Dinaric Karst and a symbol of world natural heritage. It is classified as “vulnerable” by the International Union for Conservation of Nature (IUCN) and is one of the EU priority species in need of strict protection. Due to inaccessibility of their natural underground habitat, scientific studies of the olm have been conducted mainly in captivity, where the amphibians are particularly susceptible to opportunistic microbial infections. In this report, we focused on the diversity of cultivable commensal fungi isolated from the skin of asymptomatic and symptomatic animals obtained from nature (20 specimens) and captivity (22 specimens), as well as from underground water of two karstic caves by direct water filtration and by exposure of keratin-based microbial baits and subsequent isolation from them. In total 244 fungal isolates were recovered from the animals and additional 153 isolates were obtained from water samples. Together, these isolates represented 87 genera and 166 species. Symptomatic animals were colonized by a variety of fungal species, most of them represented by a single isolate, including genera known for their involvement in chromomycosis, phaeohyphomycosis and zygomycosis in amphibians: Acremonium, Aspergillus, Cladosporium, Exophiala, Fusarium, Mucor, Ochroconis, Phialophora and Penicillium. One symptomatic specimen sampled from nature was infected by the oomycete Saprolegnia parasitica, the known causative agent of saprolegniosis. This is the first comprehensive report on cultivable skin mycobiome of this unique amphibian in nature and in captivity, with an emphasis on potentially pathogenic fungi and oomycetes.
Single Amino Acid Substitution in the DNA Repairing Gene Radiation-Sensitive 4 Contributes to Ultraviolet Tolerance of a Plant Pathogen
Authors: Wang Yan-Ping , Yang Li-Na , Feng Yuan-Yuan , Liu Songqing , Zhan Jiasui
Published: July 2022

To successfully survive and reproduce, all species constantly modify the structure and expression of their genomes to cope with changing environmental conditions including ultraviolet (UV) radiation. Thus, knowledge of species adaptation to environmental changes is a central theme of evolutionary studies which could have important implication for disease management and social-ecological sustainability in the future but is generally insufficient. Here, we investigated the evolution of UV adaptation in organisms by population genetic analysis of sequence structure, physiochemistry, transcription, and fitness variation in the radiation-sensitive 4 (RAD4) gene of the Irish potato famine pathogen Phytophthora infestans sampled from various altitudes. We found that RAD4 is a key gene determining the resistance of the pathogen to UV stress as indicated by strong phenotype-genotype-geography associations and upregulated transcription after UV exposure. We also found conserved evolution in the RAD4 gene. Only five nucleotide haplotypes corresponding to three protein isoforms generated by point mutations were detected in the 140 sequences analyzed and the mutations were constrained to the N-terminal domain of the protein. Physiochemical changes associated with non-synonymous mutations generate severe fitness penalty to mutants, which are purged out by natural selection, leading to the conserved evolution observed in the gene.
Genetic Diversity, Evolutionary Dynamics, and Pathogenicity of Ferret Badger Rabies Virus Variants in Mainland China, 2008–2018
Authors: Miao Faming , Zhao Jinghui , Li Nan , Liu Ye , Chen Teng , Mi Lijuan , Yang Jinjin , Chen Qi , Zhang Fei , Feng Jie , Li Shunfei , Zhang Shoufeng , Hu Rongliang
Published: July 2022

In contrast to dog-associated human rabies cases decline year by year due to the rabies vaccination coverage rates increase in China, ferret badger (FB, Melogale moschata)-associated human rabies cases emerged in the 1990s, and are now an increasingly recognized problem in southeast China. To investigate epidemiology, temporal evolution dynamics, transmission characterization, and pathogenicity of FB-associated rabies viruses (RABVs), from 2008 to 2018, we collected 3,622 FB brain samples in Jiangxi and Zhejiang Province, and detected 112 RABV isolates. Four FB-related lineages were identified by phylogenetic analysis (lineages A–D), the estimated Times to Most Recent Common Ancestor were 1941, 1990, 1937, and 1997 for lineages A–D, respectively. Furthermore, although no FB-associated human rabies case has been reported there apart from Wuyuan area, FB-RABV isolates are mainly distributed in Jiangxi Province. Pathogenicity of FB-RABVs was assessed using peripheral inoculation in mice and in beagles with masseter muscles, mortality-rates ranging from 20 to 100% in mice and 0 to 20% in beagles in the groups infected with the various isolates. Screening of sera from humans with FB bites and no post-exposure prophylaxis to rabies revealed that five of nine were positive for neutralizing antibodies of RABV. All the results above indicated that FB-RABV variants caused a lesser pathogenicity in mice, beagles, and even humans. Vaccination in mice suggests that inactivated vaccine or recombinant subunit vaccine products can be used to control FB-associated rabies, however, oral vaccines for stray dogs and wildlife need to be developed and licensed in China urgently.
Effects of High-Fat Diet During Childhood on Precocious Puberty and Gut Microbiota in Mice
Authors: Bo Tingbei , Liu Min , Tang Liqiu , Lv Jinzhen , Wen Jing , Wang Dehua
Published: July 2022

Precocious puberty mostly stems from endocrine disorders. However, more and more studies show that a high-fat diet (HFD) is closely related to precocious puberty, but its mechanism is unknown. Since gut microbiota is associated with hormone secretion and obesity, it inspires us to detect the mechanism of gut microbiota in triggering precocious puberty. The model of precocious puberty was established by feeding female mice with an HFD from 21 days old. After puberty, the serum hormone levels, gut microbiome sequencing, and metabolomics were collected. DNA was extracted from feces, and the V3–V4 region of the bacterial 16S rRNA gene was amplified, followed by microbial composition analysis. Subsequently, associations between precocious puberty and the microbiota were determined. We found that (1) HFD after weaning caused precocious puberty, increased serum estradiol, leptin, deoxycholic acid (DCA), and gonadotropin-releasing hormone (GnRH) in the hypothalamus; (2) Through correlation analysis, we found that GnRH was positively correlated with Desulfovibrio, Lachnoclostridium, GCA-900066575, Streptococcus, Anaerotruncus, and Bifidobacterium, suggesting that these bacteria may have a role in promoting sexual development. (3) “HFD-microbiota” transplantation promoted the precocious puberty of mice. (4) Estrogen changes the composition and proportion of gut microbiota and promotes precocious puberty. Therefore, the effect of HFD on precocious puberty is regulated by the interaction of gut microbiota and hormones.
Novel, acidic, and cold-adapted glycoside hydrolase family 8 endo-β-1,4-glucanase from an Antarctic lichen-associated bacterium, Lichenicola cladoniae PAMC 26568
Authors: Kim Do Young , Kim Jonghoon , Lee Yung Mi , Byeon Soo Min , Gwak Jeong Hae , Lee Jong Suk , Shin Dong-Ha , Park Ho-Yong
Published: July 2022

Endo-β-1,4-glucanase is a crucial glycoside hydrolase (GH) involved in the decomposition of cellulosic materials. In this study, to discover a novel cold-adapted β-1,4-D-glucan-degrading enzyme, the gene coding for an extracellular endo-β-1,4-glucanase (GluL) from Lichenicola cladoniae PAMC 26568, an Antarctic lichen (Cladonia borealis)-associated bacterium, was identified and recombinantly expressed in Escherichia coli BL21. The GluL gene (1044-bp) encoded a non-modular polypeptide consisting of a single catalytic GH8 domain, which shared the highest sequence identity of 55% with that of an uncharacterized protein from Gluconacetobacter takamatsuzukensis (WP_182950054). The recombinant endo-β-1,4-glucanase (rGluL: 38.0 kDa) most efficiently degraded sodium carboxymethylcellulose (CMC) at pH 4.0 and 45°C, and showed approximately 23% of its maximum degradation activity even at 3°C. The biocatalytic activity of rGluL was noticeably enhanced by >1.3-fold in the presence of 1 mM Mn2+ or NaCl at concentrations between 0.1 and 0.5 M, whereas the enzyme was considerably downregulated by 1 mM Hg2+ and Fe2+ together with 5 mM N-bromosuccinimide and 0.5% sodium dodecyl sulfate. rGluL is a true endo-β-1,4-glucanase, which could preferentially decompose D-cellooligosaccharides consisting of 3 to 6 D-glucose, CMC, and barley β-glucan, without other additional glycoside hydrolase activities. The specific activity (15.1 U mg–1) and kcat/Km value (6.35 mg–1 s–1mL) of rGluL toward barley β-glucan were approximately 1.8- and 2.2-fold higher, respectively, compared to its specific activity (8.3 U mg–1) and kcat/Km value (2.83 mg–1 s–1mL) toward CMC. The enzymatic hydrolysis of CMC, D-cellotetraose, and D-cellohexaose yielded primarily D-cellobiose, accompanied by D-glucose, D-cellotriose, and D-cellotetraose. However, the cleavage of D-cellopentaose by rGluL resulted in the production of only D-cellobiose and D-cellotriose. The findings of the present study imply that rGluL is a novel, acidic, and cold-adapted GH8 endo-β-1,4-glucanase with high specific activity, which can be exploited as a promising candidate in low-temperature processes including textile and food processes.
Isolation and characterization of two homolog phages infecting Pseudomonas aeruginosa
Authors: Yuanyuan Niu , Xiaobo Yang , Shang Wang , Yutong Yang , Hongrui Zhou , Chenyu Li , Bin Xue , Xi Zhang , Chen Zhao , Zhiqiang Shen , Jingfeng Wang , Yun Ling , Pingfeng Yu , Zhigang Qiu
Published: July 2022

Bacteriophages (phages) are capable of infecting specific bacteria, and therefore can be used as a biological control agent to control bacteria-induced animal, plant, and human diseases. In this study, two homolog phages (named PPAY and PPAT) that infect Pseudomonas aeruginosa PAO1 were isolated and characterized. The results of the phage plaque assay showed that PPAT plaques were transparent dots, while the PPAY plaques were translucent dots with a halo. Transmission electron microscopy results showed that PPAT (65 nm) and PPAY (60 nm) strains are similar in size and have an icosahedral head and a short tail. Therefore, these belong to the short-tailed phage family Podoviridae. One-step growth curves revealed the latent period of 20 min and burst time of 30 min for PPAT and PPAY. The burst size of PPAT (953 PFUs/infected cell) was higher than that of PPAY (457 PFUs/infected cell). Also, the adsorption rate constant of PPAT (5.97 × 10−7 ml/min) was higher than that of PPAY (1.32 × 10−7 ml/min) at 5 min. Whole-genome sequencing of phages was carried out using the Illumina HiSeq platform. The genomes of PPAT and PPAY have 54,888 and 50,154 bp, respectively. Only 17 of the 352 predicted ORFs of PPAT could be matched to homologous genes of known function. Likewise, among the 351 predicted ORFs of PPAY, only 18 ORFs could be matched to genes of established functions. Homology and evolutionary analysis indicated that PPAT and PPAY are closely related to PA11. The presence of tail fiber proteins in PPAY but not in PPAT may have contributed to the halo effect of its plaque spots. In all, PPAT and PPAY, newly discovered P. aeruginosa phages, showed growth inhibitory effects on bacteria and can be used for research and clinical purposes.
Highly Effective Markerless Genetic Manipulation of Streptococcus suis Using a Mutated PheS-Based Counterselectable Marker
Authors: Gao Guangjuan , Wei Dong , Li Gang , Chen Ping , Wu Liujun , Liu Siguo , Zhang Yueling
Published: July 2022

Streptococcus suis is an important zoonotic pathogen, however, an efficient markerless genetic manipulation system is still lacking for further physiological and pathological studies on this bacterium. Several techniques have been developed for markerless genetic manipulation of S. suis utilizing either a temperature-sensitive vector or a counterselectable markers (CSMs), however, at present, the efficiency of these techniques is not very satisfactory. In this study, we developed a strategy for markerless genetic manipulation of S. suis employing a CSM based on a conditionally lethal mutant allele of pheS, which encodes the α-subunit of phenylalanyl-tRNA synthetase (PheS). This mutant pheS, mPheS, was constructed by introducing site-directed mutations for a T261S/A315G double-substitution and a number of silent mutations to decrease its similarity with the endogenous wild type pheS gene (wtPheS). Additionally, five potentially strong promoters from S. suis were screened for their ability to drive high-level expression of mPheS, thus endowing the carrier strain with sufficient sensitivity to the phenylalanine analog p-chloro-phenylalanine (p-Cl-phe). Insertion of these P-mPheS cassettes into a vector or into the chromosomal locus via a linked erythromycin resistance gene revealed that mPheS allele driven by promoters P0530 and P1503 renders S. suis sensitive to as low as 0.01% (or 0.5 mM) of p-Cl-phe. This offers two potential CSMs for S. suis with p-Cl-phe as a counterselective agent. P1503-mPheS was revealed to be 100% efficient for counter-selection in S. suis by application in a precise gene deletion. Using P1503-mPheS as a CSM, a two-step insertion and excision strategy for markerless genetic manipulation of S. suis were developed, supplying a powerful tool for markerless genetic manipulation of S. suis.
Screening for Potential Therapeutic Agents for Non-Small Cell Lung Cancer by Targeting Ferroptosis
Authors: Zhao Xin , Cui Lijuan , Zhang Yushan , Guo Chao , Deng Lijiao , Wen Zhitong , Lu Zhihong , Shi Xiaoyuan , Xing Haojie , Liu Yunfeng , Zhang Yi
Published: July 2022

Ferroptosis is a form of non-apoptotic and iron-dependent cell death originally identified in cancer cells. Recently, emerging evidence showed that ferroptosis-targeting therapy could be a novel promising anti-tumour treatment. However, systematic analyses of ferroptosis-related genes for the prognosis of non-small cell lung cancer (NSCLC) and the development of antitumor drugs exploiting the ferroptosis process remain rare. This study aimed to identify genes related to ferroptosis and NSCLC and to initially screen lead compounds that induce ferroptosis in tumor cells. We downloaded mRNA expression profiles and NSCLC clinical data from The Cancer Genome Atlas database to explore the prognostic role of ferroptosis-related genes. Four prognosis-associated ferroptosis-related genes were screened using univariate Cox regression analysis and the lasso Cox regression analysis, which could divide patients with NSCLC into high- and low-risk groups. Then, based on differentially expressed risk- and ferroptosis-related genes, the negatively correlated lead compound flufenamic acid (FFA) was screened through the Connective Map database. This project confirmed that FFA induced ferroptosis in A549 cells and inhibited growth and migration in a dose-dependent manner through CCK-8, scratch, and immunofluorescence assays. In conclusion, targeting ferroptosis might be a therapeutic alternative for NSCLC.
Monitoring the Progression of Cell-Free Expression of Microbial Rhodopsins by Surface Enhanced IR Spectroscopy: Resolving a Branch Point for Successful/Unsuccessful Folding
Authors: Ataka Kenichi , Baumann Axel , Chen Jheng-Liang , Redlich Aoife , Heberle Joachim , Schlesinger Ramona
Published: July 2022

The translocon-unassisted folding process of transmembrane domains of the microbial rhodopsins sensory rhodopsin I (HsSRI) and II (HsSRII), channelrhodopsin II (CrChR2), and bacteriorhodopsin (HsBR) during cell-free expression has been investigated by Surface-Enhanced Infrared Absorption Spectroscopy (SEIRAS). Up to now, only a limited number of rhodopsins have been expressed and folded into the functional holoprotein in cell free expression systems, while other microbial rhodopsins fail to properly bind the chromophore all-trans retinal as indicated by the missing visible absorption. SEIRAS experiments suggest that all investigated rhodopsins lead to the production of polypeptides, which are co-translationally inserted into a solid-supported lipid bilayer during the first hour after the in-vitro expression is initiated. Secondary structure analysis of the IR spectra revealed that the polypeptides form a comparable amount of α-helical structure during the initial phase of insertion into the lipid bilayer. As the process progressed (>1 h), only HsBR exhibited a further increase and association of α-helices to form a compact tertiary structure, while the helical contents of the other rhodopsins stagnated. This result suggests that the molecular reason for the unsuccessful cell-free expression of the two sensory rhodopsins and of CrChR2 is not due to the translation process, but rather to the folding process during the post-translational period. Taking our previous observation into account that HsBR fails to form a tertiary structure in the absence of its retinal, we infer that the chromophore retinal is an integral component of the compaction of the polypeptide into its tertiary structure and the formation of a fully functional protein.
Antibody-Antigen Binding Interface Analysis in the Big Data Era
Authors: Reis Pedro B. P. S. , Barletta German P. , Gagliardi Luca , Fortuna Sara , Soler Miguel A. , Rocchia Walter
Published: July 2022

Antibodies have become the Swiss Army tool for molecular biology and nanotechnology. Their outstanding ability to specifically recognise molecular antigens allows their use in many different applications from medicine to the industry. Moreover, the improvement of conventional structural biology techniques (e.g., X-ray, NMR) as well as the emergence of new ones (e.g., Cryo-EM), have permitted in the last years a notable increase of resolved antibody-antigen structures. This offers a unique opportunity to perform an exhaustive structural analysis of antibody-antigen interfaces by employing the large amount of data available nowadays. To leverage this factor, different geometric as well as chemical descriptors were evaluated to perform a comprehensive characterization.
Sex Hormones, Sleep, and Memory: Interrelationships Across the Adult Female Lifespan
Authors: Harrington Yasmin A. , Parisi Jeanine M. , Duan Daisy , Rojo-Wissar Darlynn M. , Holingue Calliope , Spira Adam P.
Published: July 2022

As the population of older adults grows, so will the prevalence of aging-related conditions, including memory impairments and sleep disturbances, both of which are more common among women. Compared to older men, older women are up to twice as likely to experience sleep disturbances and are at a higher risk of cognitive decline and Alzheimer’s disease and related dementias (ADRD). These sex differences may be attributed in part to fluctuations in levels of female sex hormones (i.e., estrogen and progesterone) that occur across the adult female lifespan. Though women tend to experience the most significant sleep and memory problems during the peri-menopausal period, changes in memory and sleep have also been observed across the menstrual cycle and during pregnancy. Here, we review current knowledge on the interrelationships among female sex hormones, sleep, and memory across the female lifespan, propose possible mediating and moderating mechanisms linking these variables and describe implications for ADRD risk in later life.
Age-Related Eye Diseases in Individuals With Mild Cognitive Impairment and Alzheimer's Disease
Authors: Chua Jacqueline , Zhang Zheting , Wong Damon , Tan Bingyao , Kulantayan Bhavani , Sng Chelvin C. A. , Hilal Saima , Venketasubramanian Narayanaswamy , Tan Boon Yeow , Cheung Carol Y. , Garhöfer Gerhard , Popa-Cherecheanu Alina , Wong Tien Yin , Chen Christopher Li-Hsian , Schmetterer Leopold
Published: July 2022

Introduction

Alzheimer's disease (AD) and age-related eye diseases pose an increasing burden as the world's population ages. However, there is limited understanding on the association of AD/cognitive impairment, no dementia (CIND) with age-related eye diseases.

Methods

In this cross-sectional, memory clinic-based study of multiethnic Asians aged 50 and above, participants were diagnosed as AD (n = 216), cognitive impairment, no dementia (CIND) (n = 252), and no cognitive impairment (NCI) (n = 124) according to internationally accepted criteria. Retinal photographs were graded for the presence of age-related macular degeneration (AMD) and diabetic retinopathy (DR) using standard grading systems. Multivariable-adjusted logistic regression models were used to determine the associations between neurological diagnosis and odds of having eye diseases.

Results

Over half of the adults had at least one eye disease, with AMD being the most common (60.1%; n = 356), followed by DR (8.4%; n = 50). After controlling for age, sex, race, educational level, and marital status, persons with AD were more likely to have moderate DR or worse (OR = 2.95, 95% CI = 1.15–7.60) compared with NCI. In the fully adjusted model, the neurological diagnosis was not associated with AMD (OR = 0.75, 95% CI = 0.45–1.24).

Conclusion

Patients with AD have an increased odds of having moderate DR or worse, which suggests that these vulnerable individuals may benefit from specific social support and screening for eye diseases.
Increased Serum NSE and S100B Indicate Neuronal and Glial Alterations in Subjects Under 71 Years With Mild Neurocognitive Disorder/Mild Cognitive Impairment
Authors: Polyakova Maryna , Mueller Karsten , Arelin Katrin , Lampe Leonie , Rodriguez Francisca S. , Luck Tobias , Kratzsch Jürgen , Hoffmann Karl-Titus , Riedel-Heller Steffi , Villringer Arno , Schoenknecht Peter , Schroeter Matthias L.
Published: July 2022

Background

Mild cognitive impairment (MCI) is considered a pre-stage of different dementia syndromes. Despite diagnostic criteria refined by DSM-5 and a new term for MCI – “mild neurocognitive disorder” (mild NCD) – this diagnosis is still based on clinical criteria.

Methods

To link mild NCD to the underlying pathophysiology we assessed the degree of white matter hyperintensities (WMH) in the brain and peripheral biomarkers for neuronal integrity (neuron-specific enolase, NSE), plasticity (brain-derived neurotrophic factor, BDNF), and glial function (S100B) in 158 community-dwelling subjects with mild NCD and 82 healthy controls. All participants (63–79 years old) were selected from the Leipzig-population-based study of adults (LIFE).

Results

Serum S100B levels were increased in mild NCD in comparison to controls (p= 0.007). Serum NSE levels were also increased but remained non-significant after Bonferroni-Holm correction(p= 0.04). Furthermore, age by group interaction was significant for S100B. In an age-stratified sub-analysis, NSE and S100B were higher in younger subjects with mild NCD below 71 years of age. Some effects were inconsistent after controlling for potentially confounding factors. The discriminatory power of the two biomarkers NSE and S100B was insufficient to establish a pathologic threshold for mild NCD. In subjects with mild NCD, WMH load correlated with serum NSE levels (r = 0.20,p= 0.01), independently of age.

Conclusion

Our findings might indicate the presence of neuronal (NSE) and glial (S100B) injury in mild NCD. Future studies need to investigate whether younger subjects with mild NCD with increased biomarker levels are at risk of developing major NCD.
Risk of New-Diagnosed Atrial Fibrillation After Transient Ischemic Attack
Authors: Purroy Francisco , Vicente-Pascual Mikel , Arque Gloria , Begue Robert , Farre Joan , Gallego Yhovany , Gil-Villar Maria Pilar , Mauri Gerard , Montalà Nuria , Pereira Cristina , Torres-Querol Coral , Vazquez-Justes Daniel
Published: July 2022

Background

Transient ischemic attack (TIA) provides a unique opportunity to optimize secondary preventive treatments to avoid subsequent ischemic stroke (SIS). Although atrial fibrillation (AF) is the leading cause of cardioembolism in IS and anticoagulation prevents stroke recurrence (SR), limited data exists about the risk of new-diagnosed AF (NDAF) after TIA and the consequences of the diagnostic delay. The aim of our study was to determine this risk in a cohort of TIA patients with long-term follow-up.

Methods

We carried out a prospective cohort study of 723 consecutive TIA patients from January 2006 to June 2010. Median follow-up was 6.5 (5.0–9.6) years. In a subgroup of 204 (28.2%) consecutive patients, a panel of biomarkers was assessed during the first 24 h of the onset of symptoms. Multivariate analyses were performed to find out the associated factors of NDAF. Kaplan-Meier analysis was also performed to analyzed risk of SIS.

Results

NDAF was indentified in 116 (16.0%) patients: 42 (36.2%) during admission, 18 (15.5%) within first year, 29 (25%) between one and five years and 27 (23.3%) beyond 5 years. NDAF was associated with sex (female) [hazard ratio (HR) 1.61 (95% CI, 1.07- 2.41)], age [[HR 1.05 (95% CI, 1.03–1.07)], previous ischemic heart disease (IHD) [HR 1.84, (95% CI 1.15–2.97)] and cortical DWI pattern [HR 2.81 (95% CI, 1.87–4.21)]. In the Kaplan-Meier analysis, NT-proBNP ≥ 218.2 pg/ml (log-rank test P < 0.001) was associated with significant risk of NDAF during the first 5 years of follow-up. Patients with NDAF after admission and before 5 years of follow-up had the highest risk of SIS (P = 0.002).

Conclusion

The risk of NDAF after TIA is clinically relevant. We identified clinical and neuroimaging factors of NDAF. In addition, NT-proBNP was related to NDAF. Our results can be used to evaluate the benefit of long-term cardiac monitoring in selected patients.
Elevated Blood S100B Levels in Patients With Migraine: A Systematic Review and Meta-Analysis
Authors: Chu Chaojia , Zhong Rui , Cai Mengtan , Li Nan , Lin Weihong
Published: July 2022

Background:

In recent years, a growing number of researches indicate that S100B may act in migraine, but the relationship between S100B and migraine remains controversial. Therefore, the current study aimed to perform a meta-analysis to quantitatively summarize S100B levels in migraine patients.

Methods

We used Stata 12.0 software to summarize eligible studies from PubMed, EMBASE, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), and Wanfang databases. We applied standardized mean differences (SMDs) with 95% confidence intervals (95%CIs) to appraise the association between S100B and migraine.

Results

The combined results of nine case-control studies indicated that compared with healthy controls, overall migraine patients had significantly increased S100B levels in peripheral blood (SMD = 0.688, 95%CI: 0.341–1.036, P < 0.001). The S100B levels in migraineurs during ictal periods (SMD =1.123, 95%CI: 0.409–1.836, P = 0.002) and interictal periods (SMD = 0.487, 95%CI: 0313–0.661, P < 0.001), aura (SMD = 0.999, 95%CI: 0.598–1.400, P < 0.001) and without aura (SMD = 0.534, 95%CI: 0.286–0.783, P < 0.001) were significantly higher than those in the controls. The subgroup analyses by age, country, migraine assessment, and assay method of S100B also illustrated a statistically obvious association between S100B levels and migraine, indicating that age may be the most important source of heterogeneity. Sensitivity analysis showed that no individual study has a significant influence on the overall association between S100B and migraine.

Conclusion

This meta-analysis demonstrates that the level of S100B in peripheral blood of patients with migraine was significantly increased. Migraine may be associated with pathological reactions involving S100B, which is instrumental for the clinical diagnosis of migraine and therapy that considers S100B as a potential target.
Case Report: Effect of Targeted Therapy With Carbamazepine in KCNQ2 Neonatal Epilepsy
Authors: Dilena Robertino , Mauri Eleonora , Di Fonzo Alessio , Bana Cristina , Ajmone Paola Francesca , Rigamonti Claudia , Catenio Tamara , Gangi Silvana , Striano Pasquale , Fumagalli Monica
Published: July 2022

We present a family case of neonatal-onset KCNQ2-related epilepsy due to a novel intronic mutation. Three members of an Italian family (father and offspring) presented with neonatal-onset asymmetric tonic and clonic seizures with peculiar video-electroencephalography and aEEG features referring to sequential seizures. The father and the first son underwent standard of care treatments in line with current neonatal intensive care unit protocols, with a prolonged hospitalization before reaching full seizure control with carbamazepine. After the experience acquired with her family and the latest advances in the literature, the younger daughter was directly treated with carbamazepine, obtaining rapid seizure control and short hospitalization. They all had normal development. Carbamazepine is rarely administered as a first-line option in neonatal seizures. Recent evidence suggests that neonatal intensive care unit protocols should implement a trial with sodium channel blockers such as carbamazepine as first-option anti-seizure medication and a fast access to genetic testing in neonates with sequential seizures without structural brain injury or acute causes. Moreover, we report and discuss the laboratory studies performed on a novel causative intronic mutation in KCNQ2 (c.1525+5 G>A in IVS13), since pathogenicity may be difficult to prove for intronic variants.
The BERN Framework of Mind-Body Medicine: Integrating Self-Care, Health Promotion, Resilience, and Applied Neuroscience
Authors: Esch Tobias , Stefano George B.
Published: July 2022

Background: Mind-body medicine (MBM) focuses on improving our understanding of how the interactions between the brain, mind, body, and behavior can be used to promote health. In this narrative review, we present the basic principles of MBM, including the introduction of a rational framework for the implementation of MBM-based interventions. We also discuss the contributions of MBM to motivation and reward systems in the brain including those that may specifically involve the mitochondria.

Results: MBM can be used to promote health in patients with chronic diseases, especially conditions identified as lifestyle-related. MBM builds on salutogenesis, which is a paradigm that focuses on health (as opposed to disease) determinants and the development of individual resilience and coherence factors as a means to reduce stress, decrease the burden of disease, and improve the quality of life. This approach involves several well-known principles of self-healing and self-care. MBM interventions typically include behavioral modification techniques in conjunction with cognitive work focused on stress regulation, exercise, relaxation, meditation, and nutrition. We suggest the use of the acronym “BERN” (Behavior, Exercise, Relaxation, and Nutrition) to summarize the operational framework of this approach.

Discussion: Different BERN techniques act via shared autoregulatory central nervous system (CNS) reward and motivation circuitries. These systems rely on numerous neurobiological signaling pathways with overlapping effector molecules that converge, e.g., on nitric oxide (NO) as a common effector molecule. NO is critically coupled to reward physiology, stress reduction, and self-regulation as it modulates the responses of various mitochondrial, nuclear, and chromosomal processes within brain cells. NO has also been implicated in relevant outcomes (e.g., the placebo response).

Conclusions: MBM interventions typically follow the BERN model and aim to strengthen health and resilience, and reduce stress. The mechanisms of action of these processes involve the CNS reward systems and correlate with placebo and self-healing pathways.
Association of Dietary Factors With Grip Strength, Body Fat, and Prevalence of Sarcopenic Obesity in Rural Korean Elderly With Cardiometabolic Multimorbidity
Authors: Kim Jieun , Baek Younghwa , Jeong Kyoungsik , Lee Siwoo
Published: July 2022

Background and Aims

Aging accompanied by cardiometabolic multimorbidity (CM) promotes chronic low-grade inflammation, increased oxidative stress, and insulin resistance (IR), which result in loss of muscle mass and functional impairment. Better quality diets have been directly associated with muscle health and decreased risk of all-cause mortality. However, no study has investigated the relationship of dietary factors with grip strength, body composition, and prevalence of sarcopenic obesity (SO) in Korean rural residents according to their CM pattern. Therefore, we aimed to examine this association among this population.

Materials and Methods

This cross-sectional study utilized data from 932 rural residents aged ≥ 65 years. An exploratory tetrachoric factor analysis revealed four multimorbidity patterns: CM, inflammatory disease, respiratory disease, and cancer and other diseases. All participants were categorized into the CM and non-CM groups. Skeletal muscle mass and the prevalence of sarcopenia were estimated using bioelectrical impedance analysis (BIA). Dietary assessment was analyzed using a validated 106-item food frequency questionnaire. Adjusted multiple linear regression and multivariate logistic regression were employed to examine the association of dietary factors with muscle strength, quality, and SO prevalence ratio in elderly participants.

Results

The mean age of the participants was 71.8 ± 0.1 years (65.8% women). Dietary fat and protein intake were positively correlated with handgrip strength in women with CM, after adjusting for covariates (p = 0.001). Similarly, protein intake (g/kg) was positively associated with appendicular skeletal muscle mass (ASM; kg/m2) and ASM (%) in both sexes in the CM and non-CM groups. Regarding the tertiles of wheat intake (g/d), 2.1-fold increase in SO prevalence ratios [prevalence ratio (PR): 2.149, confidence intervals (CIs): 1.134–4.071] was observed in the highest tertile (T3: 269.1 g/d), compared to the lowest tertile (Q1: 8.6 g/d) in the CM group. Higher tertile of meat intake (T2: 34.8 g/d, T3: 99.5 g/d) had a 2-fold increase in SO (PR: 1.932, CIs: 1.066–3.500) compared to the lowest tertile (T1: 9.2 g/d) in the CM group.

Conclusion

Overconsumption of wheat and meat negatively impacted the development of SO, while protein intake was positively associated with grip strength and skeletal muscle mass in elderly Koreans with CM.
To Estimate Performance of Artificial Neural Network Model Based on Terahertz Spectrum: Gelatin Identification as an Example
Authors: Li Yizhang , Liu Lingyu , Wang Zhongmin , Chang Tianying , Li Ke , Xu Wenqing , Wu Yong , Yang Hua , Jiang Daoli
Published: July 2022

It is a necessity to determine significant food or traditional Chinese medicine (TCM) with low cost, which is more likely to achieve high accurate identification by THz-TDS. In this study, feedforward neural networks based on terahertz spectra are employed to predict the animal origin of gelatins, whose adaption to the mission is examined by parallel models built by random sample partition and initialization. It is found that the generalization performance of feedforward ANNs in original data is not satisfactory although prediction on trained samples can be accurate. A multivariate scattering correction is conducted to enhance prediction accuracy, and 20 additional models verify the effectiveness of such dispose. A special partition of total dataset is conducted based on statistics of parallel models, whose influence on ANN performance is investigated with another 20 models. The performance of the models is unsatisfactory because of notable differences in training and test sets according to principal component analysis. By comparing the distribution of the first two principal components before and after multivariate scattering correction, we found that the reciprocal of the minimum number of line segments required for error-free classification in 2-D feature space can be viewed as an index to describe linear separability of data. The rise of proposed linear separability would have a lower requirement for harsh parameter tuning of ANN models and tolerate random initialization. The difference in principal components of samples between a training set and a data set determines whether partition is acceptable or whether a model would have generality. A rapid way to estimate the performance of an ANN before sufficient tuning on a classification mission is to compare differences between groups and differences within groups. Given that a representative peak missing curve is discussed in this article, an analysis based on gelatin THz spectra may be helpful for studies on some other feature-less species.
Apoptotic and Necroptotic Mediators are Differentially Expressed in Mucinous and Non-Mucinous Colorectal Cancer
Authors: O’Connell Emer , Reynolds Ian S. , Lindner Andreas U. , Salvucci Manuela , O’Grady Tony , Bacon Orna , Cho Sanghee , McDonough Elizabeth , Longley Daniel , Ginty Fiona , McNamara Deborah A. , Burke John P. , Prehn Jochen H. M.
Published: July 2022

Background

Mucinous colorectal cancer (CRC) represents 10% of all CRC and is associated with chemotherapy resistance. This study aimed to determine expression of apoptosis and necroptosis mediators in mucinous CRC.

Methods

RNA gene expression data were extracted from TCGA. Protein levels in 14 mucinous and 39 non-mucinous tumors were measured by multiplexed immunofluorescence. Levels of apoptosis and necroptosis signalling proteins were analysed in SW1463 (mucinous rectal), SW837 (non-mucinous rectal), LS174T (mucinous colon) and HCT116 (non-mucinous colon) cell lines by western blot. Cell death was investigated by flow cytometry measurement of propidium iodide stained cells.

Results

High cleaved-Caspase 3 expression was noted in resected mucinous tumors. Western blot identified alterations in apoptosis proteins in mucinous CRC, most prominently downregulation of Bcl-xL protein levels (p=0.029) which was also observed at the mRNA level in patients by analysis of TCGA gene expression data (p<0.001). Treatment with 5-FU did not significantly elevate cell death in mucinous cells, while non-mucinous cells showed robust cell death responses. However, 5-FU-induced phosphorylation of MLKL in mucinous cancer cells, suggestive of a switch to necroptotic cell death signaling.

Conclusion

Apoptotic and necroptotic mediators are differentially expressed in mucinous and non-mucinous colorectal cancers and represent targets for investigation of cell death mechanisms in the mucinous subtype.
Neoadjuvant and Adjuvant Chemotherapy for Variant Histology Bladder Cancers: A Systematic Review and Meta-Analysis
Authors: Zhu Ziwei , Xiao Yunyuan , Hu Shengye , Wang Ziyuan , Zhu Zaisheng
Published: July 2022

Context

To improve the prognosis of variant histology (VH) bladder cancers, clinicians have used neoadjuvant chemotherapy (NAC) or adjuvant chemotherapy (AC) on the basis of radical cystectomy (RC). Despite some new data, the evidence remains mixed on their efficacy.

Objective

To update the current evidence on the role of NAC and AC for VH bladder cancers.

Evidence Acquisition

We searched for all studies investigating NAC or AC for bladder cancer patients with variant histology in PubMed, Embase, and the Cochrane Central Register of Controlled Trials up to December 2021. The primary end points were recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS).

Evidence Synthesis

We identified 18 reports comprising a total of 10,192 patients in the NAC studies. In patients with VH, the use of NAC did improve CSS (hazard ratio [HR] 0.74, 95% confidence interval [CI] 0.55–0.99, p = 0.044), and OS (HR 0.74, 95% CI 0.66–0.84, p = 0.000), but not RFS (HR 1.15, 95% CI 0.56–2.33, p = 0.706). Subgroup analyses demonstrated that receiving NAC was associated with better OS in sarcomatoid VH (HR 0.67, 95% CI 0.54–0.83, p = 0.000) and neuroendocrine VH (HR 0.54, 95% CI 0.43–0.68, p = 0.000). For AC, we identified eight reports comprising a total of 3254 patients. There was a benefit in CSS (HR 0.61, 95% CI 0.43–0.87, p = 0.006) and OS (HR 0.76, 95% CI 0.60–0.98, p = 0.032). Subgroup analyses demonstrated that only neuroendocrine VH had better CSS (HR 0.29, 95% CI 0.13–0.67, p = 0.174) when receiving AC.

Conclusions

NAC or AC for VH bladder cancers confers an OS and CSS benefit compared with RC alone. For NAC, the benefit was independently observed in the sarcomatoid and neuroendocrine subgroups. As for AC, only neuroendocrine subgroups improved CSS.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/, identifier CRD42021289487.