bluuebunny/crossref_metadata_2025 huggingface dataset:
The bile salt deoxycholate induces Campylobacter jejuni genetic point mutations that promote increased antibiotic resistance and fitness
Authors: Talukdar Prabhat K. , Crockett Torin M. , Gloss Lisa M. , Huynh Steven , Roberts Steven A. , Turner Kyrah L. , Lewis Sebastien T. E. , Herup-Wheeler Tristin L. , Parker Craig T. , Konkel Michael E.
Published: December 2022

Oxidative damage to DNA is a significant source of mutations in living organisms. While DNA damage must be repaired to maintain the integrity of the genome and cell survival, errors made during DNA repair may contribute to evolution. Previous work has revealed that Campylobacter jejuni growth in the presence of bile salt deoxycholate (DOC) causes an increase in reactive oxygen species and the occurrence of 8-oxo-deoxyguanosine (8-oxo-dG) DNA lesions. The fundamental goal of this project was to determine if C. jejuni growth in a medium containing DOC contributes to DNA mutations that provide a fitness advantage to the bacterium. Co-culture experiments revealed that C. jejuni growth in a DOC-supplemented medium increases the total number of ciprofloxacin-resistant isolates compared to C. jejuni grown in the absence of DOC. We recovered two individual isolates grown in a medium with DOC that had a point mutation in the gene encoding the EptC phosphoethanolamine transferase. Transformants harboring the EptC variant protein showed enhanced resistance to the antimicrobial agent polymyxin B and DOC when compared to an eptC deletion mutant or the isolate complemented with a wild-type copy of the gene. Finally, we found that the base excision repair (BER), homologous recombination repair (HRR), and nucleotide excision repair (NER) are involved in general oxidative damage repair in C. jejuni but that the BER pathway plays the primary role in the repair of the 8-oxo-dG lesion. We postulate that bile salts drive C. jejuni mutations (adaptations) and enhance bacterial fitness in animals.
Model-driven approach for the production of butyrate from CO2/H2 by a novel co-culture of C. autoethanogenum and C. beijerinckii
Authors: Benito-Vaquerizo Sara , Nouse Niels , Schaap Peter J. , Hugenholtz Jeroen , Brul Stanley , López-Contreras Ana M. , Martins dos Santos Vitor A. P. , Suarez-Diez Maria
Published: December 2022

One-carbon (C1) compounds are promising feedstocks for the sustainable production of commodity chemicals. CO2 is a particularly advantageous C1-feedstock since it is an unwanted industrial off-gas that can be converted into valuable products while reducing its atmospheric levels. Acetogens are microorganisms that can grow on CO2/H2 gas mixtures and syngas converting these substrates into ethanol and acetate. Co-cultivation of acetogens with other microbial species that can further process such products, can expand the variety of products to, for example, medium chain fatty acids (MCFA) and longer chain alcohols. Solventogens are microorganisms known to produce MCFA and alcohols via the acetone-butanol-ethanol (ABE) fermentation in which acetate is a key metabolite. Thus, co-cultivation of an acetogen and a solventogen in a consortium provides a potential platform to produce valuable chemicals from CO2. In this study, metabolic modeling was implemented to design a new co-culture of an acetogen and a solventogen to produce butyrate from CO2/H2 mixtures. The model-driven approach suggested the ability of the studied solventogenic species to grow on lactate/glycerol with acetate as co-substrate. This ability was confirmed experimentally by cultivation of Clostridium beijerinckii on these substrates in batch serum bottles and subsequently in pH-controlled bioreactors. Community modeling also suggested that a novel microbial consortium consisting of the acetogen Clostridium autoethanogenum, and the solventogen C. beijerinckii would be feasible and stable. On the basis of this prediction, a co-culture was experimentally established. C. autoethanogenum grew on CO2/H2 producing acetate and traces of ethanol. Acetate was in turn, consumed by C. beijerinckii together with lactate, producing butyrate. These results show that community modeling of metabolism is a valuable tool to guide the design of microbial consortia for the tailored production of chemicals from renewable resources.
Potential of Bacillus pumilus to directly promote plant growth
Authors: Dobrzyński Jakub , Jakubowska Zuzanna , Dybek Barbara
Published: December 2022

Plant Growth-Promoting Bacteria (PGPB) are a promising alternative to conventional fertilization. One of the most interesting PGPB strains, among the spore-forming bacteria of the phylum Firmicutes, is Bacillus pumilus. It is a bacterial species that inhabits a wide range of environments and shows resistance to abiotic stresses. So far, several PGPB strains of B. pumilus have been described, including B. pumilus LZP02, B. pumilus JPVS11, B. pumilus TUAT-1, B. pumilus TRS-3, and B. pumilus EU927414. These strains have been shown to produce a wide range of phytohormones and other plant growth-promoting substances. Therefore, they can affect various plant properties, including biometric traits, substance content (amino acids, proteins, fatty acids), and oxidative enzymes. Importantly, based on a study with B. pumilus WP8, it can be concluded that this bacterial species stimulates plant growth when the native microbiota of the inoculated soil is altered. However, there is still a lack of research with deeper insights into the structure of the native microbial community (after B. pumilus application), which would provide a better understanding of the functioning of this bacterial species in the soil and thus increase its effectiveness in promoting plant growth.
Graph neural network and multi-data heterogeneous networks for microbe-disease prediction
Authors: Gong Houwu , You Xiong , Jin Min , Meng Yajie , Zhang Hanxue , Yang Shuaishuai , Xu Junlin
Published: December 2022

The research on microbe association networks is greatly significant for understanding the pathogenic mechanism of microbes and promoting the application of microbes in precision medicine. In this paper, we studied the prediction of microbe-disease associations based on multi-data biological network and graph neural network algorithm. The HMDAD database provided a dataset that included 39 diseases, 292 microbes, and 450 known microbe-disease associations. We proposed a Microbe-Disease Heterogeneous Network according to the microbe similarity network, disease similarity network, and known microbe-disease associations. Furthermore, we integrated the network into the graph convolutional neural network algorithm and developed the GCNN4Micro-Dis model to predict microbe-disease associations. Finally, the performance of the GCNN4Micro-Dis model was evaluated via 5-fold cross-validation. We randomly divided all known microbe-disease association data into five groups. The results showed that the average AUC value and standard deviation were 0.8954 ± 0.0030. Our model had good predictive power and can help identify new microbe-disease associations. In addition, we compared GCNN4Micro-Dis with three advanced methods to predict microbe-disease associations, KATZHMDA, BiRWHMDA, and LRLSHMDA. The results showed that our method had better prediction performance than the other three methods. Furthermore, we selected breast cancer as a case study and found the top 12 microbes related to breast cancer from the intestinal flora of patients, which further verified the model’s accuracy.
Biological effects of Thymol loaded chitosan nanoparticles (TCNPs) on bacterial plant pathogen Xanthomonas campestris pv. campestris
Authors: Sreelatha Sarangapani , Kumar Nadimuthu , Rajani Sarojam
Published: December 2022

Engineered nanomaterials can provide eco-friendly alternatives for crop disease management. Chitosan based nanoparticles has shown beneficial applications in sustainable agricultural practices and effective healthcare. Previously we demonstrated that Thymol loaded chitosan nanoparticles (TCNPs) showed bactericidal activity against Xanthomonas campestris pv campestris (Xcc), a bacterium that causes black rot disease in brassica crops. Despite the progress in assessing the antibacterial action of TCNPs, the knowledge about the molecular response of Xcc when exposed to TCNPs is yet to be explored. In the present study, we combined physiological, spectroscopic and untargeted metabolomics studies to investigate the response mechanisms in Xcc induced by TCNPs. Cell proliferation and membrane potential assays of Xcc cells exposed to sub-lethal concentration of TCNPs showed that TCNPs affects the cell proliferation rate and damages the cell membrane altering the membrane potential. FTIR spectroscopy in conjunction with untargeted metabolite profiling using mass spectrometry of TCNPs treated Xcc cells revealed alterations in amino acids, lipids, nucleotides, fatty acids and antioxidant metabolites. Mass spectroscopy analysis revealed a 10–25% increase in nucleic acid, fatty acids and antioxidant metabolites and a 20% increase in lipid metabolites while a decrease of 10–20% in amino acids and carbohydrates was seen in in TCNP treated Xcc cells. Overall, our results demonstrate that the major metabolic perturbations induced by TCNPs in Xcc are associated with membrane damage and oxidative stress, thus providing information on the mechanism of TCNPs mediated cytotoxicity. This will aid towards the development of nano- based agrochemicals as an alternative to chemical pesticides in future.
Environmental changes affect the microbial release of hydrogen sulfide and methane from sediments at Boknis Eck (SW Baltic Sea)
Authors: Perner Mirjam , Wallmann Klaus , Adam-Beyer Nicole , Hepach Helmke , Laufer-Meiser Katja , Böhnke Stefanie , Diercks Isabel , Bange Hermann W. , Indenbirken Daniela , Nikeleit Verena , Bryce Casey , Kappler Andreas , Engel Anja , Scholz Florian
Published: December 2022

Anthropogenic activities are modifying the oceanic environment rapidly and are causing ocean warming and deoxygenation, affecting biodiversity, productivity, and biogeochemical cycling. In coastal sediments, anaerobic organic matter degradation essentially fuels the production of hydrogen sulfide and methane. The release of these compounds from sediments is detrimental for the (local) environment and entails socio-economic consequences. Therefore, it is vital to understand which microbes catalyze the re-oxidation of these compounds under environmental dynamics, thereby mitigating their release to the water column. Here we use the seasonally dynamic Boknis Eck study site (SW Baltic Sea), where bottom waters annually fall hypoxic or anoxic after the summer months, to extrapolate how the microbial community and its activity reflects rising temperatures and deoxygenation. During October 2018, hallmarked by warmer bottom water and following a hypoxic event, modeled sulfide and methane production and consumption rates are higher than in March at lower temperatures and under fully oxic bottom water conditions. The microbial populations catalyzing sulfide and methane metabolisms are found in shallower sediment zones in October 2018 than in March 2019. DNA-and RNA profiling of sediments indicate a shift from primarily organotrophic to (autotrophic) sulfide oxidizing Bacteria, respectively. Previous studies using data collected over decades demonstrate rising temperatures, decreasing eutrophication, lower primary production and thus less fresh organic matter transported to the Boknis Eck sediments. Elevated temperatures are known to stimulate methanogenesis, anaerobic oxidation of methane, sulfate reduction and essentially microbial sulfide consumption, likely explaining the shift to a phylogenetically more diverse sulfide oxidizing community based on RNA.
Wastewater surveillance of antibiotic-resistant bacterial pathogens: A systematic review
Authors: Tiwari Ananda , Kurittu Paula , Al-Mustapha Ahmad I. , Heljanko Viivi , Johansson Venla , Thakali Ocean , Mishra Shyam Kumar , Lehto Kirsi-Maarit , Lipponen Anssi , Oikarinen Sami , Pitkänen Tarja ,   WastPan Study Group, Heikinheimo Annamari
Published: December 2022

Infectious diseases caused by antibiotic-resistant bacterial (ARB) pathogens are a serious threat to human and animal health. The active surveillance of ARB using an integrated one-health approach can help to reduce the emergence and spread of ARB, reduce the associated economic impact, and guide antimicrobial stewardship programs. Wastewater surveillance (WWS) of ARB provides composite samples for a total population, with easy access to the mixed community microbiome. This concept is emerging rapidly, but the clinical utility, sensitivity, and uniformity of WWS of ARB remain poorly understood especially in relation to clinical evidence in sewershed communities. Here, we systematically searched the literature to identify studies that have compared findings from WWS of ARB and antibiotic resistance genes (ARG) with clinical evidence in parallel, thereby evaluating how likely WWS of ARB and ARG can relate to the clinical cases in communities. Initially, 2,235 articles were obtained using the primary search keywords, and 1,219 articles remained after de-duplication. Among these, 35 articles fulfilled the search criteria, and an additional 13 relevant articles were included by searching references in the primary literature. Among the 48 included papers, 34 studies used a culture-based method, followed by 11 metagenomics, and three PCR-based methods. A total of 28 out of 48 included studies were conducted at the single sewershed level, eight studies involved several countries, seven studies were conducted at national or regional scales, and five at hospital levels. Our review revealed that the performance of WWS of ARB pathogens has been evaluated more frequently for Escherichia coli, Enterococcus spp., and other members of the family Enterobacteriaceae, but has not been uniformly tested for all ARB pathogens. Many wastewater-based ARB studies comparing the findings with clinical evidence were conducted to evaluate the public health risk but not to relate with clinical evidence and to evaluate the performance of WWS of ARB. Indeed, relating WWS of ARB with clinical evidence in a sewershed is not straightforward, as the source of ARB in wastewater cannot be only from symptomatic human individuals but can also be from asymptomatic carriers as well as from animal sources. Further, the varying fates of each bacterial species and ARG within the sewerage make the aim of connecting WWS of ARB with clinical evidence more complicated. Therefore, future studies evaluating the performance of many AMR pathogens and their genes for WWS one by one can make the process simpler and the interpretation of results easier.
ML364 exerts the broad-spectrum antivirulence effect by interfering with the bacterial quorum sensing system
Authors: Zhang Youwen , Dong Limin , Sun Lang , Hu Xinxin , Wang Xiukun , Nie Tongying , Li Xue , Wang Penghe , Pang Pengbo , Pang Jing , Lu Xi , Yao Kaihu , You Xuefu
Published: December 2022

Antivirulence strategy has been developed as a nontraditional therapy which would engender a lower evolutionary pressure toward the development of antimicrobial resistance. However, the majority of the antivirulence agents currently in development could not meet clinical needs due to their narrow antibacterial spectrum and limited indications. Therefore, our main purpose is to develop broad-spectrum antivirulence agents that could target on both Gram-positive and Gram-negative pathogens. We discovered ML364, a novel scaffold compound, could inhibit the productions of both pyocyanin of Pseudomonas aeruginosa and staphyloxanthin of Staphylococcus aureus. Further transcriptome sequencing and enrichment analysis showed that the quorum sensing (QS) system of pathogens was mainly disrupted by ML364 treatment. To date, autoinducer-2 (AI-2) of the QS system is the only non-species-specific signaling molecule that responsible for the cross-talk between Gram-negative and Gram-positive species. And further investigation showed that ML364 treatment could significantly inhibit the sensing of AI-2 or its nonborated form DPD signaling in Vibrio campbellii MM32 and attenuate the biofilm formation across multi-species pathogens including Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae and Staphylococcus aureus. The results of molecular docking and MM/GBSA free energy prediction showed that ML364 might have higher affinity with the receptors of DPD/AI-2, when compared with DPD molecule. Finally, the in vivo study showed that ML364 could significantly improve the survival rates of systemically infected mice and attenuate bacterial loads in the organs of mice. Overall, ML364 might interfere with AI-2 quorum sensing system to exert broad-spectrum antivirulence effect both in vitro and in vivo.
Enhancement of HSA-pFSHβ production by disrupting YPS1 and supplementing N-acetyl-L-cysteine in Pichia pastoris
Authors: Luo Gang , Geng Zijian , Kuerban Buayisham , Xu Yingqing , Yang Jingjing , Liu Jiying , Li Muwang
Published: December 2022

Introduction

Pichia pastoris is widely used for the production of recombinant proteins, but the low production efficiency hinders its wide application in biopharmaceuticals. Moreover, many biopharmaceutical-like proteins are accompanied by degradation during secretory expression in P. pastoris.

Objective

In this study, we used human serum albumin and porcine follicle-stimulating hormone β (HSA-pFSHβ) fusion protein as a model protein to investigate whether YPS1 and YPT7 gene disruption and N-acetyl-L-cysteine (NAC) supplementation have synergistic effects to inhibit the degradation of recombinant proteins.

Results and discussion

Our results showed that YPS1 gene disruption reduced the degradation of intact HSA-pFSHβ and increased the yield of intact protein in the culture medium and cells without affecting the integrity of the cell wall. Moreover, the beneficial effects of YPS1 gene disruption were associated with the upregulation of the MAPK signaling pathway and maintenance of redox homeostasis. YPS1 gene disruption and NAC supplementation had synergistic effects on HSA-pFSHβ production. In addition, disruption of vacuolar morphology by YPT7 gene disruption or NH4Cl treatment affected the production of recombinant HSA-pFSHβ protein. Furthermore, YPT7 gene disruption inhibited the processing of signal peptide in high-level produced HSA-pFSHβ strain. In conclusion, our results demonstrated that YPS1 disruption could reduce the degradation of intact HSA-pFSHβ proteins, and synergistically increase the yield of intact HSA-pFSHβ with NAC supplementation. This study provided a valuable reference for reducing recombinant protein degradation and therefore improving the yield of recombinant proteins in P. pastoris.
Homozygous GRHPR C.494G>A mutation is deleterious that causes early onset of nephrolithiasis in West Bengal, India
Authors: Chatterjee Arindam , Sarkar Kunal , Bank Sarbashri , Ghosh Sudakshina , Kumar Pal Dilip , Saraf Siddharth , Wakle Dhansagar , Roy Bidyut , Chakraborty Santanu , Bankura Biswabandhu , Chattopadhyay Debprasad , Das Madhusudan
Published: December 2022

Pediatric nephrolithiasis (NL) or Kidney stone disease (KSD) is an untethered topic in Asian population. In Western countries, the annual incidence of paediatric NL is around 6–10%. Here, we present data from West Bengal, India, on lower age (LA, 0–20 years) NL and its prevalence for the first time. To discover the mutations associated with KSD, twenty-four (18 + 6) rare LA-NL patients were selected for Whole Exome Sequencing (WES) and Sanger sequencing, respectively. It was found that GRHPR c. 494G>A mutation (MZ826703) is predominant in our study cohort. This specific homozygous mutation is functionally studied for the first time directly from human peripheral mononuclear cell (PBMC) samples. Using expression study with biochemical activity and computational analysis we assumed that the mutation is pathogenic with loss of function. Moreover, three genes, AGXT, HOGA1 and GRHPR with Novel variants known to cause hyperoxaluria were found frequently in the study cohort. Our study analyses the genes and variations that cause LA-NL, as well as the molecular function of the GRHPR mutation, which may serve as a clinical marker in the population of West Bengal, Eastern India.
The Acinetobacter baumannii model can explain the role of small non-coding RNAs as potential mediators of host-pathogen interactions
Authors: Sarshar Meysam , Scribano Daniela , Palamara Anna Teresa , Ambrosi Cecilia , Masotti Andrea
Published: December 2022

Bacterial small RNAs (sRNAs) research has accelerated over the past decade, boosted by advances in RNA-seq technologies and methodologies for capturing both protein–RNA and RNA–RNA interactions. The emerging picture is that these regulatory sRNAs play important roles in controlling complex physiological processes and are required to survive the antimicrobial challenge. In recent years, the RNA content of OMVs/EVs has also gained increasing attention, particularly in the context of infection. Secreted RNAs from several bacterial pathogens have been characterized but the exact mechanisms promoting pathogenicity remain elusive. In this review, we briefly discuss how secreted sRNAs interact with targets in infected cells, thus representing a novel perspective of host cell manipulation during bacterial infection. During the last decade, Acinetobacter baumannii became clinically relevant emerging pathogens responsible for nosocomial and community-acquired infections. Therefore, we also summarize recent findings of regulation by sRNAs in A. baumannii and discuss how this emerging bacterium utilizes many of these sRNAs to adapt to its niche and become successful human pathogen.
Exploring the role of Tibetan medicinal formula Qishiwei Zhenzhu Pills (Ranasampel) against diabetes mellitus-linked cognitive impairment of db/db mice through serum pharmacochemistry and microarray data analysis
Authors: Yan Zhiyi , Zong Yonghua , Zhang Chengfei , Han Zekun , Wu Lili , Qin Lingling , Liu Tonghua
Published: December 2022

Background

Diabetes cognitive impairment (DCI) is a common diabetic central nervous system disorder that severely affects the quality of life of patients. Qishiwei Zhenzhu Pills (Ranasampel) is a valuable Tibetan medicine formula with the ability to improve cerebral blood vessels, protect nerves and improve learning and memory, which has also been widely verified in clinical and basic research. Currently, the prevention and treatment of DCI are still in the exploratory research stage, and the use of Ranasampel will provide new ideas and insights for its treatment.

Objective

This study is to explore the absorbed components in serum derived from Ranasampel using serum pharmacochemistry, then identify the potential mechanism of Ranasampel for the treatment of DCI through bioinformatics and microarray data validation.

Methods

The UPLC-Q-Exactive MS/MS-based serum pharmacochemistry method was conducted to identify the main active components in serum containing Ranasampel. Then, these components were used to predict the possible biological targets of Ranasampel and explore the potential targets in treating DCI by overlapping with differentially expressed genes (DEGs) screened from Gene Expression Omnibus datasets. Afterward, the protein–protein interaction network, enrichment analyses, hub gene identification, and co-expression analysis were used to study the potential mechanism of Ranasampel. Particularly, the hub genes and co-expression transcription factors were further validated using hippocampal expression profiles of db/db mice treated with Ranasampel, while the Morris water-maze test and H&E staining were used to assess the spatial learning and memory behaviors and histopathological changes.

Results

Totally, 40 compounds derived from Ranasampel had been identified by serum sample analysis, and 477 genes related to these identified compounds in Ranasampel, 110 overlapping genes were collected by the intersection of Ranasampel target genes and DEGs. Further comprehensive analysis and verification emphasized that the mechanism of Ranasampel treatment of DCI may be related to the improvement of learning and memory function as well as insulin resistance, hyperglycemia-induced neuronal damage, and neuroinflammation.

Conclusion

This study provided useful strategies to explore the potential material basis for compound prescriptions such as Ranasampel. These hub genes and common pathways also provided new ideas for further study of therapeutic targets of DCI and the pharmacological mechanism of Ranasampel.
Cognitive parameters can predict change of walking performance in advanced Parkinson’s disease – Chances and limits of early rehabilitation
Authors: Geritz Johanna , Welzel Julius , Hansen Clint , Maetzler Corina , Hobert Markus A. , Elshehabi Morad , Knacke Henrike , Aleknonytė-Resch Milda , Kudelka Jennifer , Bunzeck Nico , Maetzler Walter
Published: December 2022

Introduction

Links between cognition and walking performance in patients with Parkinson’s disease (PD), which both decline with disease progression, are well known. There is lack of knowledge regarding the predictive value of cognition for changes in walking performance after individualized therapy. The aim of this study is to identify relevant predictive cognitive and affective parameters, measurable in daily clinical routines, for change in quantitative walking performance after early geriatric rehabilitation.

Methods

Forty-seven acutely hospitalized patients with advanced PD were assessed at baseline (T1) and at the end (T2) of a 2-week early rehabilitative geriatric complex treatment (ERGCT). Global cognitive performance (Montreal Cognitive Assessment, MoCA), EF and divided attention (Trail Making Test B minus A, delta TMT), depressive symptoms, and fear of falling were assessed at T1. Change in walking performance was determined by the difference in quantitative walking parameters extracted from a sensor-based movement analysis over 20 m straight walking in single (ST, fast and normal pace) and dual task (DT, with secondary cognitive, respectively, motor task) conditions between T1 and T2. Bayesian regression (using Bayes Factor BF10) and multiple linear regression models were used to determine the association of non-motor characteristics for change in walking performance.

Results

Under ST, there was moderate evidence (BF10 = 7.8, respectively, BF10 = 4.4) that lower performance in the ∆TMT at baseline is associated with lower reduction of step time asymmetry after treatment (R2adj = 0.26, p ≤ 0.008, respectively, R2adj = 0.18, p ≤ 0.009). Under DT walking-cognitive, there was strong evidence (BF10 = 29.9, respectively, BF10 = 27.9) that lower performance in the ∆TMT is associated with more reduced stride time and double limb support (R2adj = 0.62, p ≤ 0.002, respectively, R2adj = 0.51, p ≤ 0.009). There was moderate evidence (BF10 = 5.1) that a higher MoCA total score was associated with increased gait speed after treatment (R2adj = 0.30, p ≤ 0.02).

Discussion

Our results indicate that the effect of ERGT on change in walking performance is limited for patients with deficits in EF and divided attention. However, these patients also seem to walk more cautiously after treatment in walking situations with additional cognitive demand. Therefore, future development of individualized treatment algorithms is required, which address individual needs of these vulnerable patients.
The effects of circadian desynchronization on alcohol consumption and affective behavior during alcohol abstinence in female rats
Authors: Meyer Christiane , Schoettner Konrad , Amir Shimon
Published: December 2022

Disruption of circadian rhythmicity distorts physiological and psychological processes and has major consequences on health and well-being. A chronic misalignment within the internal time-keeping system modulates alcohol consumption and contributes to stress-related psychiatric disorders which are known to trigger alcohol misuse and relapse. While there is growing evidence of the deleterious impact of circadian disruption on male physiology and behavior, knowledge about the effect in females remains limited. The present study aims to fill the gap by assessing the relationship between internal desynchronization and alcohol intake behavior in female rats. Female Wistar rats kept under standard 24-h, 22-h light-dark conditions, or chronic 6-h advanced phase shifts, were given intermittent access to 20% alcohol followed by an extended alcohol deprivation period. Alcohol consumption under altered light-dark (LD) conditions was assessed and emotional behavior during alcohol abstinence was evaluated. Internally desynchronization in female rats does not affect alcohol consumption but alters scores of emotionality during alcohol abstinence. Changes in affective-like behaviors were accompanied by reduced body weight gain and estrous irregularities under aberrant LD conditions. Our data suggest that internal desynchronization caused by environmental factors is not a major factor contributing to the onset and progression of alcohol abuse, but highlights the need of maintaining circadian hygiene as a supportive remedy during alcohol rehabilitation.
Theta and gamma oscillations in the rat hippocampus support the discrimination of object displacement in a recognition memory task
Authors: Neves Lívia , Lobão-Soares Bruno , Araujo Ana Paula de Castro , Furtunato Alan Michel Bezerra , Paiva Izabela , Souza Nicholy , Morais Anne Kelly , Nascimento George , Gavioli Elaine , Tort Adriano Bretanha Lopes , Barbosa Flávio Freitas , Belchior Hindiael
Published: December 2022

Episodic memory depends on the recollection of spatial and temporal aspects of past experiences in which the hippocampus plays a critical role. Studies on hippocampal lesions in rodents have shown that dentate gyrus (DG) and CA3 are necessary to detect object displacement in memory tasks. However, the understanding of real-time oscillatory activity underlying memory discrimination of subtle and pronounced displacements remains elusive. Here, we chronically implanted microelectrode arrays in adult male Wistar rats to record network oscillations from DG, CA3, and CA1 of the dorsal hippocampus while animals executed an object recognition task of high and low spatial displacement tests (HD: 108 cm, and LD: 54 cm, respectively). Behavioral analysis showed that the animals discriminate between stationary and displaced objects in the HD but not LD conditions. To investigate the hypothesis that theta and gamma oscillations in different areas of the hippocampus support discrimination processes in a recognition memory task, we compared epochs of object exploration between HD and LD conditions as well as displaced and stationary objects. We observed that object exploration epochs were accompanied by strong rhythmic activity in the theta frequency (6–12 Hz) band in the three hippocampal areas. Comparison between test conditions revealed higher theta band power and higher theta-gamma phase-amplitude coupling in the DG during HD than LD conditions. Similarly, direct comparison between displaced and stationary objects within the HD test showed higher theta band power in CA3 during exploration of displaced objects. Moreover, the discrimination index between displaced and stationary objects directly correlated with CA1 gamma band power in epochs of object exploration. We thus conclude that theta and gamma oscillations in the dorsal hippocampus support the successful discrimination of object displacement in a recognition memory task.
Once induced, it lasts for a long time: the structural and molecular signatures associated with depressive-like behavior after neonatal immune activation
Authors: Khantakova Julia N. , Bondar Natalia P. , Antontseva Elena V. , Reshetnikov Vasiliy V.
Published: December 2022

Adverse factors such as stress or inflammation in the neonatal period can affect the development of certain brain structures and have negative delayed effects throughout the lifespan of an individual, by reducing cognitive abilities and increasing the risk of psychopathologies. One possible reason for these delayed effects is the neuroinflammation caused by neonatal immune activation (NIA). Neuroinflammation can lead to disturbances of neurotransmission and to reprogramming of astroglial and microglial brain cells; when combined, the two problems can cause changes in the cytoarchitecture of individual regions of the brain. In addition, neuroinflammation may affect the hypothalamic–pituitary–adrenal (HPA) axis and processes of oxidative stress, thereby resulting in higher stress reactivity. In our review, we tried to answer the questions of whether depressive-like behavior develops after NIA in rodents and what the molecular mechanisms associated with these disorders are. Most studies indicate that NIA does not induce depressive-like behavior in a steady state. Nonetheless, adult males (but not females or adolescents of both sexes) with experience of NIA exhibit marked depressive-like behavior when exposed to aversive conditions. Analyses of molecular changes have shown that NIA leads to an increase in the amount of activated microglia and astroglia in the frontal cortex and hippocampus, an increase in oxidative-stress parameters, a change in stress reactivity of the HPA axis, and an imbalance of cytokines in various regions of the brain, but not in blood plasma, thus confirming the local nature of the inflammation. Therefore, NIA causes depressive-like behavior in adult males under aversive testing conditions, which are accompanied by local inflammation and have sex- and age-specific effects.
Geometric algebra based recurrent neural network for multi-dimensional time-series prediction
Authors: Li Yanping , Wang Yi , Wang Yue , Qian Chunhua , Wang Rui
Published: December 2022

Recent RNN models deal with various dimensions of MTS as independent channels, which may lead to the loss of dependencies between different dimensions or the loss of associated information between each dimension and the global. To process MTS in a holistic way without losing the inter-relationship among dimensions, this paper proposes a novel Long-and Short-term Time-series network based on geometric algebra (GA), dubbed GA-LSTNet. Specifically, taking advantage of GA, multi-dimensional data at each time point of MTS is represented as GA multi-vectors to capture the inherent structures and preserve the correlation of those dimensions. In particular, traditional real-valued RNN, real-valued LSTM, and the back-propagation through time are extended to the GA domain. We evaluate the performance of the proposed GA-LSTNet model in prediction tasks on four well-known MTS datasets, and compared the prediction performance with other six methods. The experimental results indicate that our GA-LSTNet model outperforms traditional real-valued LSTNet with higher prediction accuracy, providing a more accurate solution for the existing shortcomings of MTS prediction models.
Factors associated with functional disability in patients with acute stroke excluded from alteplase administration due to minor non-disabling neurological deficits
Authors: Kim Yong Jin , Choi Seok Hong , Kim Tae Young , Park Hyeon-Mi , Shin Dong Jin , Shin Dong Hoon
Published: December 2022

Background

Although the PRISMS study did not demonstrate the benefit of intravenous alteplase administration in patients with mild stroke within 3 h, about 30% of patients presenting with mild symptoms showed unfavorable functional outcomes. We investigated the factors predictive of functional disability at 90 days in patients who were excluded from alteplase administration due to the National Institutes of Health Stroke Scale (NIHSS) scores of 0–5 and a score between 0 and 2 for each NIHSS score item.

Methods

All patients were diagnosed with acute ischemic stroke or transient ischemic attack within 4.5 h of admission to a tertiary hospital and did not receive alteplase due to a minor stroke between January 2013 and December 2020. Radiological data and clinical information were collected, including baseline and discharge NIHSS scores and modified Rankin Scale (mRS) scores at 90 days. Early neurological deterioration (END) was defined as an increase of two or more NIHSS scores. We defined moderate motor weakness as a NIHSS limb motor score of more than 3 and defined a favorable outcome as a mRS score at 90 days that was 0 or 1.

Results

During the investigation period, 400 patients did not receive alteplase. END occurred significantly more frequently in patients with large artery disease (LAD) than in those with other TOAST classifications. In the multivariate regression analysis, NIHSS per 1-point increase, presenting as moderate motor weakness, and LAD were independent predictors of poor functional outcome (OR, 1.811 NIHSS per 1-point increase; 95% confidence interval [CI], 1.503–2.182; P < 0.0001; OR, 2.173 moderate motor weakness; 95% CI 1.028–4.595; P = 0.042; OR, 2.033 LAD; 95% CI 1.099–3.762; P = 0.024, respectively).

Conclusion

Moderate motor weakness presentation and LAD may be important factors associated with poor functional outcomes in patients with acute stroke excluded from alteplase administration due to mild symptoms.
Cerebellum–Cerebrum paired target magnetic stimulation on balance function and brain network of patients with stroke: A functional near-infrared spectroscopy pilot study
Authors: Xia Yifei , Tang Xinwei , Hu Ruiping , Liu Jue , Zhang Qun , Tian Shan , Wang Weining , Li Ce , Zhu Yulian
Published: December 2022

Transcranial magnetic stimulation (TMS) modulation over the cerebellum, primary motor cortex, and supplementary motor cortex individually can improve the balance function of patients with stroke. However, whether their combination could have a better balance modulation effect is uncertain. Therefore, we hypothesized that performing TMS over a combination of these targets can regulate the balance function of patients with stroke. We compared the effects of one-session TMS on eye-open and eye-closed balance conditions in patients with stroke, using different target pairs of unilateral cerebellar (CB-single), cerebellar–primary motor cortex (CB-M1), and cerebellar–supplementary motor area (CB-SMA) targets. A total of 31 patients with stroke were enrolled and randomly divided into three groups to receive single sessions of intermittent theta burst stimulation each. Functional near-infrared spectrum data on resting and standing task states (eye-open and eye-closed) and center of pressure parameters (eye-open and eye-closed) were collected before and after the intervention. Compared with the results in the CB-single group, five intergroup differences in the changes in the center of pressure parameters in the CB-M1 group and two significant differences in the CB-SMA group were observed after one session of intermittent theta burst stimulation. In the CB-SMA group, 12 out of the 14 parameters improved significantly in the EC condition after the intervention. Meanwhile, the functional near-infrared spectrum results showed that the CB-SMA group exhibited a significant inhibitory pattern in the resting-state functional connectivity, which was not observed in the other two groups. In conclusion, we believe that paired targeting of the CB-SMA can reshape the brain network and improve the balance function of patients with stroke.
Efficacy and safety of endovascular treatment in patients older than 90 with acute ischemic stroke: A retrospective cohort study
Authors: Friedman Itamar , Naftali Jonathan , Pardo Keshet , Findler Michael , Barnea Rani , Brauner Ran , Perlow Alin , Auriel Eitan , Raphaeli Guy
Published: December 2022

Background

Endovascular treatment (EVT) for acute ischemic stroke (AIS) with large vessel occlusion (LVO) is the standard of care treatment today. Although elderly patients comprise the majority of stroke patients, octogenarians and non-agenarians are often poorly represented or even excluded in clinical trials. We looked at the safety and efficacy of EVT for AIS with LVO in patients over 90 (Non-agenarians), in comparison to patients aged 80–89 (Octogenarians) and to patients younger than 80 years (<80yrs).

Methods

A retrospective analysis of patients who underwent EVT in a single stroke center during 2015–2019. Patients were divided into three subgroups based on their age: Non-agenarians, Octogenarians, and patients <80 yrs. The groups were compared based on baseline characteristics and stroke variables. In addition, we compared clinical and radiological outcomes including functional outcomes measured by the modified ranking scale (mRS) at day 90, symptomatic intracranial hemorrhage (sICH), and mortality.

Results

Three hundred and forty seven patients were included, 20 (5.7%) of them were non-agenarians, 96 (27.7%) were octogenarians and 231 (66.6%) were <80 yrs. No statistically significant differences were found between groups regarding baseline characteristics, cardiovascular risk factors, stroke variables, or successful revascularization rates. Puncture to recanalization time intervals showed an age-related non-significant increase between the groups with a median time of 67.8, 51.6, and 40.2 min of the non-agenarian, octogenarian, and <80 yrs groups, respectively (p-value = 0.3). Favorable outcome (mRS 0–2) was 15% in non-agenarians vs. 13.54% in octogenarians (p-value = 1) and 40.2% in <80 yrs. sICH occurred among 5% of non-agenarians, compared to 4% among octogenarians (p-value = 1) and 2.6% in <80 yrs. The mortality rate at 3 months was significantly higher (55%) in non-agenarians compared to octogenarians (28%) (p-value = 0.03) and to <80 yrs (19.48%).

Conclusion

EVT in nonagenarians demonstrated a high rate of successful revascularization, whilst also showing an increased rate of sICH when compared to octogenarians. Mortality rates showed an age-related correlation. Although further studies are needed to clarify the patient selection algorithm and identify sub-groups of elderly patients that could benefit from EVT, we showed that some patients do benefit from EVT therefore exclusion should not be based on age alone.
Associations between the use of β-adrenoceptor acting drugs and the risk of dementia in older population
Authors: Cui Shishuang , Fang Fang , Cui Peijing , Jiang Qianwen , Xu Shaoqing , Xu Zhihong , Hu Jia'An , Li Feika
Published: December 2022

Objective

Age-related decline within the noradrenergic system is associated with reduced cognition. The β-adrenoceptors are widely expressed in the brain as well as in the peripheral. Medications targeting β-adrenoceptor activity have been widely used in older adults. The aim of this study was to explore the associations between β-adrenoceptor acting drugs and the risk of dementia in the older population.

Methods

The subjects' information was collected from the electronic medical record (EMR) database. A propensity score matching strategy was conducted to select control participants for users of β2-agonists or β-antagonists. Logistic regression analysis was performed to estimate the risk of dementia with the use of β2-agonists or β-antagonists.

Results

A total of 1,429 participants in the EMR database were included in the study. The use of β2-agonists was strongly associated with a decreased risk of dementia [OR = 0.324, 95% confidence interval (CI): 0.149–0.707, P = 0.005]. This decreased risk showed a statistically significant inverse time-dependent pattern (Ptrend = 0.014). However, the use of non-selective β-antagonists significantly correlated with an increased dementia risk (OR = 1.961, 95% CI: 1.144–3.359, P = 0.014), although no time-dependent manner was found (Ptrend = 0.220). There was no association between selective β1-antagonists usage and dementia risk (OR = 1.114, P = 0.625).

Conclusion

The use of β-adrenoceptor acting drugs seems to be associated with the risk of dementia. Pharmacological interventions modulating β2-adrenoceptor activity might be a potential target in therapeutics for dementia.
Cerebral vascular function following the acute consumption of caffeinated artificially- and sugar sweetened soft drinks in healthy adults
Authors: Reed Emma L. , Worley Morgan L. , Kueck Paul J. , Pietrafasa Leonard D. , Schlader Zachary J. , Johnson Blair D.
Published: December 2022

Chronic consumption of sugar- and artificially-sweetened beverages (SSB and ASB) are associated with an increased risk of stroke but it is unclear how acute consumption influences cerebral vascular function.

Purpose: We hypothesized that: (1) acute consumption of SSB and ASB would augment dynamic cerebral autoregulation (dCA) and attenuate cerebral vascular reactivity to hypercapnia (CVRCO2) compared to water; and (2) dCA and CVRCO2 would be attenuated with SSB compared to ASB and water.

Methods: Twelve healthy adults (age: 23 ± 2 years, four females) completed three randomized trials where they drank 500 ml of water, SSB (Mountain Dew®), or ASB (Diet Mountain Dew®). We measured mean arterial pressure (MAP), middle and posterior cerebral artery blood velocities (MCAv and PCAv), and end-tidal CO2 tension (PETCO2). Cerebral vascular conductance was calculated as cerebral artery blood velocity/MAP (MCAc and PCAc). Twenty min after consumption, participants completed a 5 min baseline, and in a counterbalanced order, a CVRCO2 test (3%, 5%, and 7% CO2 in 3 min stages) and a dCA test (squat-stand tests at 0.10 Hz and 0.05 Hz for 5 min each) separated by 10 min. CVRCO2 was calculated as the slope of the linear regression lines of MCAv and PCAv vs. PETCO2. dCA was assessed in the MCA using transfer function analysis. Coherence, gain, and phase were determined in the low frequency (LF; 0.07–0.2 Hz) and very low frequency (VLF; 0.02–0.07 Hz).

Results: MCAv and MCAc were lower after SSB (54.11 ± 12.28 cm/s, 0.58 ± 0.15 cm/s/mmHg) and ASB (51.07 ± 9.35 cm/s, 0.52 ± 1.0 cm/s/mmHg) vs. water (62.73 ± 12.96 cm/s, 0.67 ± 0.11 cm/s/mmHg; all P < 0.035), respectively. PCAc was also lower with the ASB compared to water (P = 0.007). MCA CVRCO2 was lower following ASB (1.55 ± 0.38 cm/s/mmHg) vs. water (2.00 ± 0.57 cm/s/mmHg; P = 0.011) but not after SSB (1.90 ± 0.67 cm/s/mmHg; P = 0.593). PCA CVRCO2 did not differ between beverages (P > 0.853). There were no differences between beverages for coherence (P ≥ 0.295), gain (P ≥ 0.058), or phase (P ≥ 0.084) for either frequency.

Discussion: Acute consumption of caffeinated SSB and ASB resulted in lower intracranial artery blood velocity and conductance but had a minimal effect on cerebral vascular function as only MCA CVRCO2 was altered with the ASB compared to water.
The function of p53 and its role in Alzheimer’s and Parkinson’s disease compared to age-related macular degeneration
Authors: Wolfrum Peter , Fietz Agnes , Schnichels Sven , Hurst José
Published: December 2022

The protein p53 is the main human tumor suppressor. Since its discovery, extensive research has been conducted, which led to the general assumption that the purview of p53 is also essential for additional functions, apart from the prevention of carcinogenesis. In response to cellular stress and DNA damages, p53 constitutes the key point for the induction of various regulatory processes, determining whether the cell induces cell cycle arrest and DNA repair mechanisms or otherwise cell death. As an implication, aberrations from its normal functioning can lead to pathogeneses. To this day, neurodegenerative diseases are considered difficult to treat, which arises from the fact that in general the underlying pathological mechanisms are not well understood. Current research on brain and retina-related neurodegenerative disorders suggests that p53 plays an essential role in the progression of these conditions as well. In this review, we therefore compare the role and similarities of the tumor suppressor protein p53 in the pathogenesis of Alzheimer’s (AD) and Parkinson’s disease (PD), two of the most prevalent neurological diseases, to the age-related macular degeneration (AMD) which is among the most common forms of retinal degeneration.