bluuebunny/crossref_metadata_2025 huggingface dataset:
Metagenomic Insights Into the Microbial Assemblage Capable of Quorum Sensing and Quorum Quenching in Particulate Organic Matter in the Yellow Sea
Authors: Su Ying , Yang Yuanzhi , Zhu Xiao-Yu , Zhang Xiao-Hua , Yu Min
Published: January 2021

Quorum sensing (QS) is a density-dependent communicating mechanism that allows bacteria to regulate a wide range of biogeochemical important processes and could be inhibited by quorum quenching (QQ). Increasing researches have demonstrated that QS can affect the degradation of particulate organic matter (POM) in the photic zone. However, knowledge of the diversity and variation of microbial QS and QQ systems in sinking POM is scarce. Here, POM samples were collected from surface seawater (SW), bottom seawater (BW), and surficial sediment (SS) in the Yellow Sea of China. 16S rRNA gene amplicon and metagenome sequencing were performed to analyze the community structure of particle-associated microorganisms and distribution of QS genes [acylated homoserine lactone (AHL) synthesizing gene luxI and AHL sensing gene luxR] and QQ genes (genes encoding for AHL lactonase and acylase) in POM. Shifting community structures were observed at different sampling depths, with an increase of microbial abundance and diversity from SW to BW. Along with the variation of microbial communities, the abundances of luxI and luxR decreased slightly but were restored or even exceeded when POM arrived at SS. Comparatively, abundances of AHL lactonase and acylase remained constant during the transportation process from SW to BW but increased dramatically in SS. Correlation tests indicated that abundances of luxI and luxR were positively correlated with temperature, while those of AHL acylase were positively correlated with depth, SiO42–, PO43–, and NO3–, but negatively correlated with temperature and pH. According to phylogenetic analyses, the retrieved QS and QQ genes are more diverse and distinctive than ever experimentally identified. Besides, the vertical transmission of QS and QQ genes along with POM sinking was observed, which could be one of the key factors leading to the prevalence of QS and QQ genes in marine ecosystems. Overall, our results increase the current knowledge of QS and QQ metabolic pathways in marine environment and shed light on the intertwined interspecies relationships to better investigate their dynamics and ecological roles in POM cycling.
Evaluation of the Immunochromatographic NG-Test Carba 5, RESIST-5 O.O.K.N.V., and IMP K-SeT for Rapid Detection of KPC-, NDM-, IMP-, VIM-type, and OXA-48-like Carbapenemase Among Enterobacterales
Authors: Han Renru , Guo Yan , Peng Mingjia , Shi Qingyu , Wu Shi , Yang Yang , Zheng Yonggui , Yin Dandan , Hu Fupin
Published: January 2021

Background

Enterobacterales are the most common pathogens for nosocomial infections. The emergence and spread of KPC, NDM, and OXA-48-like carbapenemase-producing Enterobacterales with their extensively drug-resistant characteristics have posed great threats to public health. This study aimed to evaluate the performance of NG-test Carba 5, RESIST-5 O.O.K.N.V., and IMP K-SeT for rapid detection of five carbapenemases (KPC, NDM, VIM, IMP, and OXA-48-like) among Enterobacterales.

Methods

A total of 186 carbapenem-resistant Enterobacterales clinical isolates and 29 reference strains were used in this study. Carbapenemase genes were confirmed by PCR and DNA sequencing. The sensitivities and specificities of these assays were calculated utilizing the VassarStats software.

Results

For clinical isolates, the NG-test Carba 5 detected KPC, NDM, OXA-48-like, IMP, and VIM in less than 15 min with the sensitivity and specificity of 100% and 100%, respectively. The RESIST-5 O.O.K.N.V. detected KPC, NDM, OXA-48-like, and VIM with the sensitivity and specificity of 99.4 and 100%. The IMP K-SeT detected all of the IMP producers (6/6). For reference strains, the sensitivity and specificity of NG-test Carba 5, RESIST-5 O.O.K.N.V., and IMP K-SeT were all 100 and 100%, respectively.

Conclusion

As efficient, rapid, and convenient diagnostic methods, NG-test Carba 5, RESIST-5 O.O.K.N.V., and IMP K-SeT could help to simplify the complex routine workflow for detecting carbapenemases. Rapid and accurate identification of carbapenemase is of significance for both epidemiological and infection control purposes.
Proteomic Analysis of Auricularia auricula-judae Under Freezing Treatment Revealed Proteins and Pathways Associated With Melanin Reduction
Authors: Li Jiawen , Li Ziwei , Zhao Tong , Yan Xiufeng , Pang Qiuying
Published: January 2021

Auricularia auricula-judae is an edible nutrient-rich mushroom, which is a traditional medicinal resource in China. It is known that environment stimuli will affect the production of melanin by A. auricula-judae, but the mechanism of the effects of freezing treatment on melanin accumulation remains unknown. In the present study, the synthesis of melanin in A. auricula-judae was analyzed by physiological assays and a proteomics approach. Our findings showed that a longer freezing treatment causes a lighter color of A. auricula-judae fruiting bodies. The proteomic analysis showed that proteins involved in glycolysis/gluconeogenesis, tyrosine metabolism, ribosome, and arginine biosynthesis might contribute to the color differences in the A. auricula-judae after freezing treatment. This work will be expected to provide valuable information on the physiological and molecular mechanisms of freezing treatment on the color quality of A. auricula-judae.
Rv1717 Is a Cell Wall - Associated β-Galactosidase of Mycobacterium tuberculosis That Is Involved in Biofilm Dispersion
Authors: Bharti Suman , Maurya Rahul Kumar , Venugopal Umamageswaran , Singh Radhika , Akhtar Md. Sohail , Krishnan Manju Yasoda
Published: January 2021

Understanding the function of conserved hypothetical protein (CHP)s expressed by a pathogen in the infected host can lead to better understanding of its pathogenesis. The present work describes the functional characterization of a CHP, Rv1717 of Mycobacterium tuberculosis (Mtb). Rv1717 has been previously reported to be upregulated in TB patient lungs. Rv1717 belongs to the cupin superfamily of functionally diverse proteins, several of them being carbohydrate handling proteins. Bioinformatic analysis of the amino acid sequence revealed similarity to glycosyl hydrolases. Enzymatic studies with recombinant Rv1717 purified from Escherichia coli showed that the protein is a β-D-galactosidase specific for pyranose form rather than the furanose form. We expressed the protein in Mycobacterium smegmatis (Msm), which lacks its ortholog. In MsmRv1717, the protein was found to localize to the cell wall (CW) with a preference to the poles. MsmRv1717 showed significant changes in colony morphology and cell surface properties. Most striking observation was its unusual Congo red colony morphotype, reduced ability to form biofilms, pellicles and autoagglutinate. Exogenous Rv1717 not only prevented biofilm formation in Msm, but also degraded preformed biofilms, suggesting that its substrate likely exists in the exopolysaccharides of the biofilm matrix. Presence of galactose in the extracellular polymeric substance (EPS) has not been reported before and hence we used the galactose-specific Wisteria floribunda lectin (WFL) to test the same. The lectin extensively bound to Msm and Mtb EPS, but not the bacterium per se. Purified Rv1717 also hydrolyzed exopolysaccharides extracted from Msm biofilm. Eventually, to decipher its role in Mtb, we downregulated its expression and demonstrate that the strain is unable to disperse from in vitro biofilms, unlike the wild type. Biofilms exposed to carbon starvation showed a sudden upregulation of Rv1717 transcripts supporting the potential role of Rv1717 in Mtb dispersing from a deteriorating biofilm.
Characteristics of Carbapenemase-Producing Klebsiella pneumoniae Isolated in the Intensive Care Unit of the Largest Tertiary Hospital in Bangladesh
Authors: Okanda Takashi , Haque Anwarul , Koshikawa Takuro , Islam Amirul , Huda Qumrul , Takemura Hiromu , Matsumoto Tetsuya , Nakamura Shigeki
Published: January 2021

For addressing the issue of antimicrobial drug resistance in developing countries, it is important to investigate the characteristics of carbapenemase-producing organisms. We aimed to genetically characterize a carbapenemase-producingKlebsiella pneumoniae(CPKP) isolated in the intensive care unit of a tertiary hospital in Bangladesh. The number of CPKP isolates were 43/145 (30%), of which pandrug-resistant (PDR) strains were 14%. These carbapenemases were New Delhi metallo-beta-lactamase (NDM)-1 (53%), NDM-5 (14%), oxacillinase (OXA)-181 (12%), OXA-232 (10%), NDM-5 + OXA-181 (5%), and NDM-5 + OXA-232 (2%). Many CPKP isolates harbored a variety of resistance genes, and the prevalence of 16S rRNA methyltransferase was particularly high (91%). The 43 CPKP isolates were classified into 14 different sequence types (STs), and the common STs were ST34 (26%), ST147 (16%), ST11 (9%), ST14 (9%), ST25 (7%), and ST231 (7%). In this study, PDR strains were of three types, ST147, ST231, and ST14, and their PDR rates were 57, 33, and 25%, respectively. The spread of the antimicrobial drug resistance of CPKP in Bangladesh was identified. In particular, the emergence of PDR is problem, and there may be its spread as a superbug of antimicrobial treatment.
The PhoPQ Two-Component System Is the Major Regulator of Cell Surface Properties, Stress Responses and Plant-Derived Substrate Utilisation During Development of Pectobacterium versatile-Host Plant Pathosystems
Authors: Kravchenko Uljana , Gogoleva Natalia , Kalubaka Nastassia , Kruk Alla , Diubo Yuliya , Gogolev Yuri , Nikolaichik Yevgeny
Published: January 2021

Pectobacterium versatile (formerly P. carotovorum) is a recently defined species of soft rot enterobacteria capable of infecting many plant hosts and damaging different tissues. Complex transcriptional regulation of virulence properties can be expected for such a versatile pathogen. However, the relevant information is available only for related species and is rather limited. The PhoPQ two-component system, originally described in pectobacteria as PehRS, was previously shown to regulate a single gene, pehA. Using an insertional phoP mutant of Pectobacterium versatile (earlier—P. carotovorum), we demonstrate that PhoP regulates at least 115 genes with a majority of them specific for pectobacteria. The functions performed by PhoP-controlled genes include degradation, transport and metabolism of plant-derived carbon sources (polygalacturonate, arabinose-containing polysaccharides and citrate), modification of bacterial cell envelope and stress resistance. We also demonstrated PhoP involvement in establishing the order of plant cell wall decomposition and utilisation of the corresponding breakdown products. Based on experimental data and in silico analysis, we defined a PhoP binding site motif and provided proof for its universality in enteric bacteria. Scanning P. versatile genome for the locations of this motif suggested a much larger PhoP regulon enriched with the genes important for a plant pathogen, which makes PhoP a global virulence regulator. Potential PhoP targets include many regulatory genes and PhoP control over one of them, expI, was confirmed experimentally, highlighting the link between the PhoPQ two-component and quorum sensing systems. High concentrations of calcium and magnesium ions were found to abolish the PhoPQ-dependent transcription activation but did not relieve repression. Reduced PhoP expression and minimisation of PhoP dependence of regulon members’ expression in P. versatile cells isolated from potato tuber tissues suggest that PhoPQ system is a key switch of expression levels of multiple virulence-related genes fine-tuned to control the development of P. versatile-host plant pathosystem.
ParC, a New Partitioning Protein, Is Necessary for the Active Form of ParA From Myxococcus pMF1 Plasmid
Authors: Sheng Duohong , Chen Xiaojing , Li Yajie , Wang Jingjing , Zhuo Li , Li Yuezhong
Published: January 2021

The ParABS partitioning system, a main driver of DNA segregation in bacteria, employs two proteins, ParA and ParB, for plasmid partition. The pMF1 plasmid from Myxococcus fulvus 124B02 has a par operon encoding a small acidic protein, ParC, in addition to type I ParA and ParB homologs. Here, we show that expression of parC upstream of parA (as in the natural case), but not ectopic expression, is essential for the plasmid inheritance in Myxococcus cells. Co-expression of parC upstream of parA was determined to form a soluble ParC–ParA heterodimer at a 1:1 ratio, while individual expression of parA or co-expression of parA with ectopic parC formed insoluble ParA proteins. Purified ParA proteins alone had no ATPase activity and was easily dimerized, while mixing ParA with ParC formed the ParC–ParA heterodimer with the ATPase and polymerization activities. Fusing ParC and ParA also produced soluble proteins and some chimeras restored the ATPase activity and plasmid inheritance. The results highlight that proximal location of parC before parA is critical to realize the functions of ParA in the partition of Myxococcus plasmid pMF1 and shed light on a new mechanism to realize a protein function by two separate proteins.
A Targeted Sequencing Assay for Serotyping Escherichia coli Using AgriSeq Technology
Authors: Elder Jacob R. , Fratamico Pina M. , Liu Yanhong , Needleman David S. , Bagi Lori , Tebbs Robert , Allred Adam , Siddavatam Prasad , Suren Haktan , Gujjula Krishna Reddy , DebRoy Chitrita , Dudley Edward G. , Yan Xianghe
Published: January 2021

The gold standard method for serotypingEscherichia colihas relied on antisera-based typing of the O- and H-antigens, which is labor intensive and often unreliable. In the post-genomic era, sequence-based assays are potentially faster to provide results, could combine O-serogrouping and H-typing in a single test, and could simultaneously screen for the presence of other genetic markers of interest such as virulence factors. Whole genome sequencing is one approach; however, this method has limited multiplexing capabilities, and only a small fraction of the sequence is informative for subtyping or identifying virulence potential. A targeted, sequence-based assay and accompanying software for data analysis would be a great improvement over the currently available methods for serotyping. The purpose of this study was to develop a high-throughput, molecular method for serotypingE. coliby sequencing the genes that are required for production of O- and H-antigens, as well as to develop software for data analysis and serotype identification. To expand the utility of the assay, targets for the virulence factors, Shiga toxins (stx1, andstx2) and intimin (eae) were included. To validate the assay, genomic DNA was extracted from O-serogroup and H-type standard strains and from Shiga toxin-producingE. coli, the targeted regions were amplified, and then sequencing libraries were prepared from the amplified products followed by sequencing of the libraries on the Ion S5™ sequencer. The resulting sequence files were analyzedviathe SeroType Caller™ software for identification of O-serogroup, H-type, and presence ofstx1, stx2, andeae. We successfully identified 169 O-serogroups and 41 H-types. The assay also routinely detected the presence ofstx1a,c,d(3 of 3 strains),stx2c−e,g(8 of 8 strains),stx2f(1 strain), andeae(6 of 6 strains). Taken together, the high-throughput, sequence-based method presented here is a reliable alternative to antisera-based serotyping methods forE. coli.
Development of an Automated Chemiluminescence Assay System for Quantitative Measurement of Multiple Anti-SARS-CoV-2 Antibodies
Authors: Kubo Sousuke , Ohtake Norihisa , Miyakawa Kei , Jeremiah Sundararaj Stanleyraj , Yamaoka Yutaro , Murohashi Kota , Hagiwara Eri , Mihara Takahiro , Goto Atsushi , Yamazaki Etsuko , Ogura Takashi , Kaneko Takeshi , Yamanaka Takeharu , Ryo Akihide
Published: January 2021

Objectives

Serological tests for COVID-19 have been instrumental in studying the epidemiology of the disease. However, the performance of the currently available tests is plagued by the problem of variability. We have developed a high-throughput serological test capable of simultaneously detecting total immunoglobulins (Ig) and immunoglobulin G (IgG) against nucleocapsid protein (NP) and spike protein (SP) and report its performance in detecting COVID-19 in clinical samples.

Methods

We designed and prepared reagents for measuring NP-IgG, NP-Total Ig, SP-IgG, and SP-Total Ig (using N-terminally truncated NP (ΔN-NP) or receptor-binding domain (RBD) antigen) dedicated automated chemiluminescent enzyme immunoassay analyzer AIA-CL1200. After determining the basal thresholds based on 17 sera obtained from confirmed COVID-19 patients and 600 negative sera, the clinical validity of the assay was evaluated using independent 202 positive samples and 1,000 negative samples from healthy donors.

Results

All of the four test parameters showed 100% specificity individually (1,000/1,000; 95%CI, 99.63–100). The sensitivity of the assay increased proportionally to the elapsed time from symptoms onset, and all the tests achieved 100% sensitivity (153/153; 95%CI, 97.63–100) after 13 days from symptoms onset. NP-Total Ig was the earliest to attain maximal sensitivity among the other antibodies tested.

Conclusion

Our newly developed serological testing exhibited 100% sensitivity and specificity after 13 days from symptoms onset. Hence, it could be used as a reliable method for accurate detection of COVID-19 patients and to evaluate seroprevalence and possibly for surrogate assessment of herd immunity.
Pandemics Throughout History
Authors: Piret Jocelyne , Boivin Guy
Published: January 2021

The emergence and spread of infectious diseases with pandemic potential occurred regularly throughout history. Major pandemics and epidemics such as plague, cholera, flu, severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) have already afflicted humanity. The world is now facing the new coronavirus disease 2019 (COVID-19) pandemic. Many infectious diseases leading to pandemics are caused by zoonotic pathogens that were transmitted to humans due to increased contacts with animals through breeding, hunting and global trade activities. The understanding of the mechanisms of transmission of pathogens to humans allowed the establishment of methods to prevent and control infections. During centuries, implementation of public health measures such as isolation, quarantine and border control helped to contain the spread of infectious diseases and maintain the structure of the society. In the absence of pharmaceutical interventions, these containment methods have still been used nowadays to control COVID-19 pandemic. Global surveillance programs of water-borne pathogens, vector-borne diseases and zoonotic spillovers at the animal-human interface are of prime importance to rapidly detect the emergence of infectious threats. Novel technologies for rapid diagnostic testing, contact tracing, drug repurposing, biomarkers of disease severity as well as new platforms for the development and production of vaccines are needed for an effective response in case of pandemics.
Conspecific Presence Improves Episodic-Like Memory in Rats
Authors: de França Malheiros Maria Augustta Sobral , Castelo-Branco Rochele , de Medeiros Paulo Henrique Santos , de Lima Marinho Pedro Emmílio , da Silva Rodrigues Meurer Ywlliane , Barbosa Flávio Freitas
Published: January 2021

A number of studies have provided evidence that animals, including rats, remember past episodes. However, few experiments have addressed episodic-like memory from a social perspective. In the present study, we evaluated Wistar rats in the WWWhen/ELM task as single setups and in dyads, applying a long retention interval. We also investigated behaviors that could subserve the emergence of this type of memory. We found that only rats tested in the social setting were able to recollect an integrated episodic-like memory that lasted 24 h. Additionally, rats in dyads presented higher levels of exploration during the task. When exposed to the testing environment, the dyads exhibited affiliative behavior toward each other and presented fewer anxiety-like responses. Our findings indicate that the presence of a conspecific could act as a facilitating factor in memory evaluations based on spontaneous exploration of objects and provide empirical support for applying more naturalistic settings in investigations of episodic-like memory in rats.
Origins, Development, and Compartmentation of the Granule Cells of the Cerebellum
Authors: Consalez G. Giacomo , Goldowitz Daniel , Casoni Filippo , Hawkes Richard
Published: January 2021

Granule cells (GCs) are the most numerous cell type in the cerebellum and indeed, in the brain: at least 99% of all cerebellar neurons are granule cells. In this review article, we first consider the formation of the upper rhombic lip, from which all granule cell precursors arise, and the way by which the upper rhombic lip generates the external granular layer, a secondary germinal epithelium that serves to amplify the upper rhombic lip precursors. Next, we review the mechanisms by which postmitotic granule cells are generated in the external granular layer and migrate radially to settle in the granular layer. In addition, we review the evidence that far from being a homogeneous population, granule cells come in multiple phenotypes with distinct topographical distributions and consider ways in which the heterogeneity of granule cells might arise during development.
Altered Percent Amplitude of Fluctuation in Healthy Subjects After 36 h Sleep Deprivation
Authors: Zeng Bingliang , Zhou Jian , Li Zicong , Zhang Hua , Li Zongliang , Yu Peng
Published: January 2021

Objective: To investigate regional brain activity alteration in healthy subjects in a sleep deprivation (SD) status relative to a rested wakefulness status using a percent amplitude of fluctuation (PerAF) method.

Methods: A total of 20 healthy participants (12 males, 8 females; age, 22.25 ± 1.12 years) were recruited. All participants underwent attention tests and resting-state functional MRI scans during rested wakefulness before SD and after 36 h SD, respectively. The PerAF method was applied to identify SD-related regional brain activity alteration. A ROC curve was conducted to evaluate the ability of the PerAF method in distinguishing different sleep statuses. The relationships between SD-induced brain alterations and attention deficits were determined by Pearson correlation analysis.

Results: SD resulted in a 2.23% decrease in accuracy rate and an 8.82% increase in reaction time. SD was associated with increased PerAF differences in the bilateral visual cortex and bilateral sensorimotor cortex, and was associated with decreased PerAF differences in bilateral dorsolateral prefrontal cortex and bilateral cerebellum posterior lobe. These SD-induced brain alterations exhibited a high discriminatory power of extremely high AUC values (0.993–1) in distinguishing the two statuses. The accuracy rate positively correlated with the bilateral cerebellum posterior lobe, and bilateral dorsolateral prefrontal cortex, and negatively correlated with the bilateral sensorimotor cortex.

Conclusions: Acute SD could lead to an ~8% attention deficit, which was associated with regional brain activity deficits. The PerAF method might work as a potential sensitivity biomarker for identifying different sleep statuses.
Can Extra Daytime Light Exposure Improve Well-Being and Sleep? A Pilot Study of Patients With Glaucoma
Authors: Kawasaki Aki , Udry Morgane , El Wardani Mohamad , Münch Mirjam
Published: January 2021

Glaucoma damages retinal ganglion cells, including intrinsically photosensitive retinal ganglion cells (ipRGCs). These cells modulate various non-visual physiological and psychological functions which are modulated by light. In patients with glaucoma, we assessed the effect of daily bright light exposure (LE) on several melanopsin-dependent functions, such as the pupil constriction, circadian rest-activity cycles, sleep and subjective well-being including relaxation, alertness and mood. Twenty patients participated in the study (9 women, 11 men, mean age = 67.6 ± 7.5 y). Pupillometry was performed before the LE weeks and repeated on the last day of LE. The post-illumination pupil response (PIPR) was calculated as a proxy for melanopsin-dependent activation. Participants continuously wore an activity monitor and self-assessed sleep quality, well-being and visual comfort for 7 days before and during 4 weeks of daily bright LE (30 min to 10,000 lux polychromatic bright white light). After the LE, there was a significantly greater PIPR and higher subjective sleep quality when compared to the pre-LE week (p < 0.05), but no significant changes in 24-h rhythms or sleep parameters. A greater PIPR was correlated with an increase in circadian amplitude and higher inter-daily stability (derived from rest-activity cycles; p < 0.05). In a small group of patients with glaucoma, scheduled daily bright light exposure could improve subjective sleep quality. These findings highlight the importance to evaluate and maintain non-visual functions at different levels in patients with progressive loss of ipRGCs.
The Relationship Between Ankle Proprioception and Functional Mobility in People With Parkinson's Disease: A Cross-Sectional Study
Authors: Wang Yejun , Witchalls Jeremy , Preston Elisabeth , Wang Zhen , Zhuang Jie , Waddington Gordon , Adams Roger , Han Jia
Published: January 2021

Previous research has found ankle proprioception to be impaired in people with Parkinson's disease (PD). However, the relationship between ankle proprioception and functional mobility in people with PD has not been fully investigated. The purpose of this study was to examine whether ankle proprioception is related to the functional mobility of people with PD. Forty-two participants with mild to moderate PD volunteered. Ankle proprioceptive acuity was measured in standing, by using active movement extent discrimination assessment (AMEDA). Functional mobility measures included the timed-up-and-go test (TUG), 30 s sit-to-stand test (30s-STS) and 10-meter walking test (10MWT). Step length and step cadence were recorded during the 10MWT. No significant correlation was found between ankle proprioceptive discrimination scores and any mobility performance measure in people with PD (−0.20<r<0.04, all p > 0.05). However, ankle proprioception scores were significantly correlated with step length (r = 0.38, p < 0.05) and step cadence (r = −0.30, p < 0.05), and were significantly and negatively correlated with the stage of modified Hoehn and Yahr (rho = −0.53, p < 0.01). The lack of relationship between ankle proprioceptive acuity and functional mobility in PD suggests that people with PD may be more limited by reduced sensorimotor integration or may rely more on other sensory input, rather than ankle proprioception, to achieve functional mobility, a finding consistent with sensory reweighting theory. In addition, poorer ankle proprioceptive acuity was associated with decreased step length and increased step cadence, suggesting that the shuffling gait observed in PD may be related to impaired ankle proprioception, which has important clinical implications for gait retraining in people with PD. Given that ankle proprioception was significantly and negatively correlated with the stage of modified Hoehn and Yahr, it may warrant being used as an objective biomarker to monitor the progression of PD.
A Hybrid Strategy for Patients With Complex Cerebral Aneurysm: STA–MCA Bypass in Combination With Endovascular Embolization
Authors: Wang Gang , Zhang Xi'an , Gou Yanxia , Wen Yunyu , Zhang Guozhong , Li Mingzhou , Zhang Shichao , Yin Yanyi , Chen Siyuan , Qi Songtao , Feng Wenfeng
Published: January 2021

Objective: This work aims to present our experience of patients with complex cerebral aneurysm treated with a hybrid approach: superficial temporal artery–middle cerebral artery (STA–MCA) bypass in combination with endovascular exclusion of the aneurysm.

Method: Patients with aneurysms deemed unclippable and uncoilable were included. All patients were treated with a hybrid approach. After STA–MCA bypass, the parent artery was temporarily occluded. If the intraoperative motor evoked potential (MEP) and somatosensory evoked potential (SEP) waveforms remain normal and last for 30 min, the aneurysm and te parent artery will be embolized permanently with detachable balloons or coils.

Results: A total of 20 patients with 22 aneurysms were included in this study. There were 13 women and 7 men, with an average age of 42.5 years. Intraoperative angiography showed the good patency of all the STA grafts, and neither SEP nor MEP abnormalities were detected. After the parent artery and the aneurysm were occluded, the intraoperative angiography showed an immediately successful exclusion of the aneurysm in 20 aneurysms and immediate contrast stasis in two. All patients recovered uneventfully without ischemic or hemorrhagic complication. Angiography at 6-month follow-up showed the total obliteration in 20 aneurysms. Two aneurysms showed residuals and were recoiled. All STA grafts showed a good patency, and the mean graft flow was 124.2 ml/min.

Conclusion: STA–MCA bypass in combination with endovascular exclusion is an appropriate option for patients with complex cerebral aneurysms that are not amenable to direct surgical clipping or endovascular embolization.
Acute Injection of Omega-3 Triglyceride Emulsion Provides Very Similar Protection as Hypothermia in a Neonatal Mouse Model of Hypoxic-Ischemic Brain Injury
Authors: Manual Kollareth Denny Joseph , Zirpoli Hylde , Ten Vadim S. , Deckelbaum Richard J.
Published: January 2021

Therapeutic hypothermia (HT) is a currently accepted treatment for neonatal asphyxia and is a promising strategy in adult stroke therapy. We previously reported that acute administration of docosahexaenoic acid (DHA) triglyceride emulsion (tri-DHA) protects against hypoxic-ischemic (HI) injury in neonatal mice. We questioned if co-treatment with HT and tri-DHA would achieve synergic effects in protecting the brain from HI injury. Neonatal mice (10-day old) subjected to HI injury were placed in temperature-controlled chambers for 4 h of either HT (rectal temperature 31–32°C) or normothermia (NT, rectal temperature 37°C). Mice were treated with tri-DHA (0.375 g tri-DHA/kg bw, two injections) before and 1 h after initiation of HT. We observed that HT, beginning immediately after HI injury, reduced brain infarct volume similarly to tri-DHA treatment (~50%). Further, HT delayed 2 h post-HI injury provided neuroprotection (% infarct volume: 31.4 ± 4.1 vs. 18.8 ± 4.6 HT), while 4 h delayed HT did not protect against HI insult (% infarct volume: 30.7 ± 5.0 vs. 31.3 ± 5.6 HT). HT plus tri-DHA combination treatment beginning at 0 or 2 h after HI injury did not further reduce infarct volumes compared to HT alone. Our results indicate that HT offers similar degrees of neuroprotection against HI injury compared to tri-DHA treatment. HT can only be provided in tertiary care centers, requires intense monitoring and can have adverse effects. In contrast, tri-DHA treatment may be advantageous in providing a feasible and effective strategy in patients after HI injury.
Case Report: Anti-LGI1 Limbic Encephalitis Associated With Anti-thyroid Autoantibodies
Authors: Otiniano-Sifuentes Ricardo , Cuba Antezana Anali , De La Cruz Ramirez Walter F. , Pacheco-Barrios Kevin , Segura Chavez Darwin A.
Published: January 2021

Anti-LGI1 encephalitis is an autoimmune encephalitis with antibodies against leucine-rich glioma-inactivated 1 (LGI1), first described in 2010. It is a non-frequent and poorly understood entity that represents the second most frequent cause of autoimmune encephalitis. This entity is characterized by the presence of limbic encephalitis, hyponatremia, and faciobrachial dystonic seizures. Herein, we present the case of a male patient with an onset of epileptic seizures (generalized tonic-clonic seizure), and involuntary dystonic movements that affect the right side of his face and right upper limb associated with mental disorder, and affectation of higher functions. The electroencephalogram showed continuous generalized slowing of the background activity. The brain magnetic resonance imaging showed signal hyperintensity at the level of both mesial temporal lobes and hippocampi and in the head of the right caudate nucleus. Anti-thyroglobulin antibodies were positive, and he was initially diagnosed as Hashimoto's encephalopathy (HE). However, the response to corticosteroids was not completed as it is usually observed in HE. For that, antibodies for autoimmune encephalitis were tested, and the anti-LGI1 antibodies were positive in serum and cerebrospinal fluid. HE is an important differential diagnosis to consider. Furthermore, the presence of Anti-thyroglobulin antibodies should not be taken as the definitive diagnostic criteria, since these antibodies could be associated with other autoimmune encephalopathies, which include in addition to anti-LGI1, anti-NMDA and anti-Caspr2.
Increased Brain Iron Detection by Voxel-Based Quantitative Susceptibility Mapping in Type 2 Diabetes Mellitus Patients With an Executive Function Decline
Authors: Li Jing , Zhang Qihao , Zhang Nan , Guo Lingfei
Published: January 2021

Purpose

Brain iron accumulation has been suggested as a pathomechanism in patients with type 2 diabetes mellitus (T2DM) with cognitive impairment. This research aims to examine the total-brain pattern of iron accumulation in relation to executive function decline in patients with T2DM by voxel-based quantitative susceptibility mapping (QSM) analysis.

Materials and Methods

A total of 32 patients with T2DM and 34 age- and sex-matched healthy controls (HCs) were enrolled in this study. All participants underwent brain magnetic resonance examination, and 48 individuals underwent cognitive function assessments. Imaging data were collected with three-dimensional fast low-angle shot sequences to achieve magnitude as well as phase images. Using voxel-based QSM analysis, we compared the voxel-wise susceptibility values of the whole brain among groups and explored whether the susceptibility values had correlations with cognitive data.

Results

Among the 66 participants, cognitive function was estimated in 23 patients with T2DM (11 males and 12 females; average age, 64.65 ± 8.44 years) and 25 HCs (13 males and 12 females; average age, 61.20 ± 7.62 years). T2DM patients exhibited significantly (t = 4.288, P < 0.001) lower Montreal Cognitive Assessment (MoCA) scores [T2DM, 27 (27, 28); HCs, 29 (28, 29); normal standard ≥ 26)] and higher Trail-making Test (TMT)-A/TMT-B scores [71 (51, 100)/185 (149, 260)] than HCs [53 (36.5, 63.5)/150 (103, 172.5)] (Z = 2.612, P = 0.009; Z = 2.797, P = 0.005). Subjects with T2DM showed significantly higher susceptibility values than HCs in the caudate/putamen/pallidum, frontal inferior triangular gyrus, and precentral gyrus on the right hemisphere. In contrast (HC > T2DM), no region showed a significant difference in susceptibility values between the groups. The correlation analysis between susceptibility values and cognitive function scores was tested by voxel-based susceptibility value with sex and age as covariates. After multiple comparison correction, in T2DM patients, the left thalamus showed a significant relationship with TMT-A (R2 = 0.53, P = 0.001). The right thalamus and left thalamus showed a significant relationship with TMT-B (R2 = 0.35, P = 0.019; and R2 = 0.38, P = 0.017, respectively). In HCs, the cluster of right precentral/middle frontal gyrus/inferior frontal gyrus/inferior triangular gyrus showed a significant relationship with TMT-B (R2 = 0.59, P = 0.010). No relationship was found between the susceptibility values with MoCA in the brain region in both two groups.

Conclusion

Patients with T2DM presented declined cognitive assessments and elevated iron deposition in the striatum and frontal lobe, suggesting that executive function decline in T2DM might be associated with the cerebral iron burden and that changes in susceptibility values may represent a latent quantitative imaging marker for early assessment of cognitive decline in patients with T2DM.
Neuroprotective Effect of Maternal Resveratrol Supplementation in a Rat Model of Neonatal Hypoxia-Ischemia
Authors: Dumont Ursule , Sanchez Stéphane , Repond Cendrine , Beauvieux Marie-Christine , Chateil Jean-François , Pellerin Luc , Bouzier-Sore Anne-Karine , Roumes Hélène
Published: January 2021

Neonatal hypoxia-ischemia (nHI) is a major cause of death or subsequent disabilities in infants. Hypoxia-ischemia causes brain lesions, which are induced by a strong reduction in oxygen and nutrient supply. Hypothermia is the only validated beneficial intervention, but not all newborns respond to it and today no pharmacological treatment exists. Among possible therapeutic agents to test,trans-resveratrol is an interesting candidate as it has been reported to exhibit neuroprotective effects in some neurodegenerative diseases. This experimental study aimed to investigate a possible neuroprotection by resveratrol in rat nHI, when administered to the pregnant rat female, at a nutritional dose. Several groups of pregnant female rats were studied in which resveratrol was added to drinking water either during the last week of pregnancy, the first week of lactation, or both. Then, 7-day old pups underwent a hypoxic-ischemic event. Pups were followed longitudinally, using both MRI and behavioral testing. Finally, a last group was studied in which breastfeeding females were supplemented 1 week with resveratrol just after the hypoxic-ischemic event of the pups (to test the curative rather than the preventive effect). To decipher the molecular mechanisms of this neuroprotection, RT-qPCR and Western blots were also performed on pup brain samples. Data clearly indicated that when pregnant and/or breastfeeding females were supplemented with resveratrol, hypoxic-ischemic offspring brain lesions were significantly reduced. Moreover, maternal resveratrol supplementation allowed to reverse sensorimotor and cognitive deficits caused by the insult. The best recoveries were observed when resveratrol was administered during both gestation and lactation (2 weeks before the hypoxic-ischemic event in pups). Furthermore, neuroprotection was also observed in the curative group, but only at the latest stages examined. Our hypothesis is that resveratrol, in addition to the well-known neuroprotective benefitsviathe sirtuin’s pathway (antioxidant properties, inhibition of apoptosis), has an impact on brain metabolism, and more specifically on the astrocyte-neuron lactate shuttle (ANLS) as suggested by RT-qPCR and Western blot data, that contributes to the neuroprotective effects.
Grewia asiatica Berry Juice Diminishes Anxiety, Depression, and Scopolamine-Induced Learning and Memory Impairment in Behavioral Experimental Animal Models
Authors: Imran Imran , Javaid Sana , Waheed Aroosa , Rasool Muhammad Fawad , Majeed Abdul , Samad Noreen , Saeed Hamid , Alqahtani Faleh , Ahmed Mohammed M. , Alaqil Faten Abdullah
Published: January 2021

Grewia asiatica L. fruit natively called phalsa is a popular berry of Pakistan and widely consumed in the form of fresh juices and carbonated drinks in the summer season. The berry is enriched with antioxidants such as phenols, flavonoids, anthocyanins, and vitamin C. Scientifically, it is the least explored berry in terms of neuromodulatory activities, and therefore, in the designed study, chronically fed rats with the different dilutions (5%−30%) of fruit juice were subjected to behavioral assessment for anxiety, depression, and cognition (spatial memory) followed by biochemical analysis of isolated brains. Results revealed a prominent impact of 20 and 30% dilutions of fruit exudate as treated animals showed anxiolytic behavior to central zone (P < 0.05) of open field test (OFT) and open arms of elevated plus maze (EPM) (P < 0.05) in anxiety models. Overall, immobility of rats treated with a higher concentration of exudate in forced swim test (FST) was reduced (P < 0.05) presenting antidepressant-like activity. Moreover, in learning and memory experimental models, the treated animals reversed scopolamine-induced amnesic effects as evident from improved step-through latencies (P < 0.05 vs. scopolamine; passive avoidance test), spontaneous alternation behavior (P < 0.05 vs. scopolamine; Y-maze test), discrimination index (P < 0.05 vs. scopolamine; novel object recognition test), and escape latencies (P < 0.05 vs. scopolamine; Morris water maze). Biochemical studies of isolated brains from treated rats demonstrated significantly elevated levels of superoxide dismutase and glutathione peroxidase (P < 0.05), whereas levels of acetylcholinesterase and malondialdehyde level (P < 0.05) were reduced, indicating its potential to reduce oxidative damage in the brain and modulation with the cholinergic system. The outcomes of studies support the benefits of phytoconstituents possessed by G. asiatica fruit in the amelioration of neurological disorders that could be due to their antioxidative capacity or due to interaction with GABAergic, serotonergic, and cholinergic systems in the brain.
Impact of a Fermented High-Fiber Rye Diet on Helicobacter pylori and Cardio-Metabolic Risk Factors: A Randomized Controlled Trial Among Helicobacter pylori-Positive Chinese Adults
Authors: Xue Kun , Liu Yuwei , Iversen Kia Nøhr , Mazidi Mohsen , Qu Zheng , Dong Chenglin , Jin Tayi , Hallmans Göran , Åman Per , Johansson Anders , He Gengsheng , Landberg Rikard
Published: January 2021

Background: High dietary fiber intake has been associated with reduced risk of Helicobacter pylori infection and co-morbidities such as gastric cancer but also with reduced risk of cardiovascular disease. It has been suggested that fermented rye could affect Helicobacter pylori bacterial load and that high- fiber rye may be superior to wheat for improvement of several cardiometabolic risk factors, but few long-term interventions with high fiber rye foods have been conducted.

Objective: To examine the effect of high-fiber wholegrain rye foods with added fermented rye bran vs. refined wheat on Helicobacter pylori infection and cardiometabolic risk markers in a Chinese population with a low habitual consumption of high fiber cereal foods.

Design: A parallel dietary intervention was set up and 182 normal- or overweight men and women were randomized to consume wholegrain rye products containing fermented rye bran (FRB) or refined wheat (RW) for 12 weeks. Anthropometric measurements, fasting blood sample collection and 13C-urea breath test (13C-UBT) were performed at baseline and after 6 and 12 weeks of intervention as well as 12 weeks after the end of the intervention.

Results: No difference between diets on Helicobacter pylori bacterial load measured by 13C-UBT breath test or in virulence factors of Helicobacter pylori in blood samples were found. Low density lipoprotein cholesterol (LDL-C) and high sensitivity C-reactive protein (hs-CRP) were significantly lower in the FRB group, compared to the RW group after 12 weeks of intervention. The intervention diets did not affect markers of glucose metabolism or insulin sensitivity.

Conclusions: While the results of the present study did not support any effect of FRB on Helicobacter pylori bacterial load, beneficial effects on LDL-C and hs-CRP were clearly shown. This suggest that consumption of high fiber rye foods instead of refined wheat could be one strategy for primary prevention of cardiovascular disease.

Clinical Trial Registration: The trial was registered at www.clinicaltrials.gov, Identifier: NCT03103386.
Immunosenescence in Testicular Cancer Survivors: Potential Implications of Cancer Therapies and Psychological Distress
Authors: De Padova Silvia , Urbini Milena , Schepisi Giuseppe , Virga Alessandra , Meggiolaro Elena , Rossi Lorena , Fabbri Francesco , Bertelli Tatiana , Ulivi Paola , Ruffilli Federica , Casadei Chiara , Gurioli Giorgia , Rosti Giovanni , Grassi Luigi , De Giorgi Ugo
Published: January 2021

Testicular cancer (TC) is the most frequent solid tumor diagnosed in young adult males. Although it is a curable tumor, it is frequently associated with considerable short-term and long-term morbidity. Both biological and psychological stress experienced during cancer therapy may be responsible for stimulating molecular processes that induce premature aging and deterioration of immune system (immunosenescence) in TC survivors, leading to an increased susceptibility to infections, cancer, and autoimmune diseases. Immunosenescence is a remodeling of immune cell populations with inversion of the CD4:CD8 ratio, accumulation of highly differentiated memory cells, shrinkage of telomeres, shift of T-cell response to Th2 type, and release of pro-inflammatory signals. TC survivors exposed to chemotherapy show features of immunological aging, including an increase in memory T-cells (CD4+ and CD8+) and high expression of the senescence biomarker p16INK4a in CD3+ lymphocytes. However, the plethora of factors involved in the premature aging of TC survivors make the situation more complex if we also take into account the psychological stress and hormonal changes experienced by patients, as well as the high-dose chemotherapy and hematopoietic stem cell transplantation that some individuals may be required to undergo. The relatively young age and the long life expectancy of TC patients bear witness to the importance of improving quality of life and of alleviating long-term side-effects of cancer treatments. Within this context, the present review takes an in-depth look at the molecular mechanisms of immunosenescence, describing experimental evidence of cancer survivor aging and highlighting the interconnected relationship between the many factors modulating the aging of the immune system of TC survivors.
Metabolic Reprogramming Induces Immune Cell Dysfunction in the Tumor Microenvironment of Multiple Myeloma
Authors: Wu Shaojie , Kuang Huixian , Ke Jin , Pi Manfei , Yang Dong-Hua
Published: January 2021

Tumor cells rewire metabolism to meet their increased nutritional demands, allowing the maintenance of tumor survival, proliferation, and expansion. Enhancement of glycolysis and glutaminolysis is identified in most, if not all cancers, including multiple myeloma (MM), which interacts with a hypoxic, acidic, and nutritionally deficient tumor microenvironment (TME). In this review, we discuss the metabolic changes including generation, depletion or accumulation of metabolites and signaling pathways, as well as their relationship with the TME in MM cells. Moreover, we describe the crosstalk among metabolism, TME, and changing function of immune cells during cancer progression. The overlapping metabolic phenotype between MM and immune cells is discussed. In this sense, targeting metabolism of MM cells is a promising therapeutic approach. We propose that it is important to define the metabolic signatures that may regulate the function of immune cells in TME in order to improve the response to immunotherapy.