bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional Analysis of the NucS/EndoMS of the Hyperthermophilic Archaeon Sulfolobus islandicus REY15A
Authors: Ahmad Sohail , Huang Qihong , Ni Jinfeng , Xiao Yuanxi , Yang Yunfeng , Shen Yulong
Published: December 2020

EndoMS is a recently identified mismatch specific endonuclease in Thermococcales of Archaea and Mycobacteria of Bacteria. The homologs of EndoMS are conserved in Archaea and Actinobacteria, where classic MutS-MutL-mediated DNA mismatch repair pathway is absent or non-functional. Here, we report a study on the in vitro mismatch cleavage activity and in vivo function of an EndoMS homolog (SisEndoMS) from Sulfolobus islandicus REY15A, the model archaeon belonging to Crenarchaeota. SisEndoMS is highly active on duplex DNA containing G/T, G/G, and T/T mismatches. Interestingly, the cleavage activity of SisEndoMS is stimulated by the heterotrimeric PCNAs, and when Mn2+ was used as the co-factor instead of Mg2+, SisEndoMS was also active on DNA substrates containing C/T or A/G mismatches, suggesting that the endonuclease activity can be regulated by ion co-factors and accessory proteins. We compared the spontaneous mutation rate of the wild type strain REY15A and ∆endoMS by counter selection against 5-fluoroorotic acid (5-FOA). The endoMS knockout mutant had much higher spontaneous mutation rate (5.06 × 10−3) than that of the wild type (4.6 × 10−6). A mutation accumulation analysis also showed that the deletion mutant had a higher mutation occurrence than the wild type, with transition mutation being the dominant, suggesting that SisEndoMS is responsible for mutation avoidance in this hyperthermophilic archaeon. Overexpression of the wild type SisEndoMS in S. islandicus resulted in retarded growth and abnormal cell morphology, similar to strains overexpressing Hje and Hjc, the Holliday junction endonucleases. Transcriptomic analysis revealed that SisEndoMS overexpression led to upregulation of distinct gene including the CRISPR-Cas IIIB system, methyltransferases, and glycosyltransferases, which are mainly localized to specific regions in the chromosome. Collectively, our results support that EndoMS proteins represent a noncanonical DNA repair pathway in Archaea. The mechanism of the mismatch repair pathway in Sulfolobus which have a single chromosome is discussed.
Stroke Mortality Attributable to Low Fruit Intake in China: A Joinpoint and Age-Period-Cohort Analysis
Authors: Luo Lisha , Jiang Junfeng , Yu Chuanhua , Zhao Mingjuan , Wang Yunyun , Li Quanlei , Jin Yinghui
Published: December 2020

Stroke is the first leading cause of death in China, and low fruit intake is suggested to be one of the most important risk factors for stroke mortality. However, the trends of stroke mortality attributable to low fruit intake remain unclear in China. Therefore, this study aimed to investigate the long-term trends of stroke mortality attributable to low fruit intake by sex in China during 1990–2017. Data were obtained from the Global Burden of Disease 2017 study; the annual percentage change (APC) and average annual percentage change (AAPC) were estimated by joinpoint regression analysis, and the net age, period, and cohort effects were estimated using the age–period–cohort model with an intrinsic estimator algorithm (APC-IE). The crude mortality rates (CMRs) increased for males and decreased for females from 1990 to 2017. The age-standardized mortality rates (ASMRs) for both males and females showed consecutive significant declines from 1990 to 2017. By APC analysis, substantially increasing age effects were presented from 25 to 79 years for both sexes. The independent period and cohort effects progressively decreased during the entire period for both sexes, with a faster decrease for females than for males. Males and elder groups were the high-risk population for stroke mortality caused by low fruit intake. Although the mortality risk showed a decreasing trend, the fruit intake was still low for the Chinese population. Therefore, effective strategies and global awareness are essential to improve the current situation of low fruit intake, thereby preventing and reducing the stroke mortality risk caused by low fruit intake in China.
Exploring the Impact of Obesity on Skeletal Muscle Function in Older Age
Authors: Morgan Paul T. , Smeuninx Benoit , Breen Leigh
Published: December 2020

Sarcopenia is of important clinical relevance for loss of independence in older adults. The prevalence of obesity in combination with sarcopenia (“sarcopenic-obesity”) is increasing at a rapid rate. However, whilst the development of sarcopenia is understood to be multi-factorial and harmful to health, the role of obesity from a protective and damaging perspective on skeletal muscle in aging, is poorly understood. Specifically, the presence of obesity in older age may be accompanied by a greater volume of skeletal muscle mass in weight-bearing muscles compared with lean older individuals, despite impaired physical function and resistance to anabolic stimuli. Collectively, these findings support a potential paradox in which obesity may protect skeletal muscle mass in older age. One explanation for these paradoxical findings may be that the anabolic response to weight-bearing activity could be greater in obese vs. lean older individuals due to a larger mechanical stimulus, compensating for the heightened muscle anabolic resistance. However, it is likely that there is a complex interplay between muscle, adipose, and external influences in the aging process that are ultimately harmful to health in the long-term. This narrative briefly explores some of the potential mechanisms regulating changes in skeletal muscle mass and function in aging combined with obesity and the interplay with sarcopenia, with a particular focus on muscle morphology and the regulation of muscle proteostasis. In addition, whilst highly complex, we attempt to provide an updated summary for the role of obesity from a protective and damaging perspective on muscle mass and function in older age. We conclude with a brief discussion on treatment of sarcopenia and obesity and a summary of future directions for this research field.
Time-Restricted Feeding Reduces the Detrimental Effects of a High-Fat Diet, Possibly by Modulating the Circadian Rhythm of Hepatic Lipid Metabolism and Gut Microbiota
Authors: Ye Yuqian , Xu Haopeng , Xie Zhibo , Wang Lun , Sun Yuning , Yang Huayu , Hu Dandan , Mao Yilei
Published: December 2020

Background: Time-restricted feeding, also known as intermittent fasting, can confer various beneficial effects, especially protecting against obesity, and related metabolic disorders, but little is known about the underlying mechanisms. Therefore, the present study aims to investigate the effects of time-restricted feeding on the circadian rhythm of gut microbiota and hepatic metabolism.

Methods: Eight-week-old male Kunming mice received either a normal diet ad libitum, a high-fat diet ad libitum, or a high-fat diet restricted to an 8-h temporal window per day for an experimental period of 8 weeks. Weight gain and calorie intake were measured weekly. Serum metabolites, hepatic sections and lipid metabolites, gut microbiota, and the hepatic expression of Per1, Cry1, Bmal1, SIRT1, SREBP, and PPARα were measured at the end of the experimental period. The composition of gut microbiota and the expression of hepatic genes were compared between four timepoints.

Results: Mice that received a time-restricted high-fat diet had less weight gain, milder liver steatosis, and lower hepatic levels of triglycerides than mice that received a high-fat diet ad libitum (p < 0.05). The numbers of Bacteroidetes and Firmicutes differed between mice that received a time-restricted high-fat diet and mice that received a high-fat diet ad libitum (p < 0.05). Mice fed a time-restricted high-fat diet showed distinct circadian rhythms of hepatic expression of SIRT1, SREBP, and PPARα compared with mice fed a normal diet ad libitum, as well as the circadian rhythm of the abundance of Bacteroidetes and Firmicutes.

Conclusions: Time-restricted feeding is associated with better metabolic conditions, perhaps owing to alterations in gut microbiota and the circadian pattern of molecules related to hepatic lipid metabolism, which were first to report.
Clinical Features and Outcomes Analysis of Surgical Resected Pulmonary Large-Cell Neuroendocrine Carcinoma With Adjuvant Chemotherapy
Authors: Shen Yinchen , Hu Fang , Li Changhui , Xu Jianlin , Zhong Runbo , Zhang Xueyan , Chu Tianqing , Han Baohui
Published: December 2020

Objective

Large-cell neuroendocrine carcinoma (LCNEC) is a rare subtype of pulmonary cancer with poor survival. Optimal adjuvant chemotherapy for resected LCNEC is controversial till now; clinical features together with the prognostic factors in LCNEC should be clarified better.

Methods

Clinicopathological characteristics, driven genes’ status (EGFR, ALK, and ROS1), adjuvant chemotherapy strategy for 94 surgical resected LCNECs were extracted from digital database, tumor relapse or progression, and survival were analyzed with clinical profiles.

Results

Driven gene mutants were scarce in LCNEC, 8.3% (4/48) samples harbored EGFR mutations, 5.8% (3/52) with ALK positive, and none of ROS1 positive. A total of 44 patients suffered tumor relapse or progression during follow-up. Tumor/lymph node (N) stage, serum carcinoembryonic antigen (CEA) level before surgery, different adjuvant chemotherapies were associated with tumor relapse (P < 0.05); poorer disease-free survival (DFS) appeared in N2/stage III, serum CEA positive and pemetrexed based chemotherapy (P < 0.05); for overall survival (OS) analysis, the T/tumor stage, serum positive CEA/neuron-specific enolase (NSE) at baseline were associated with worse OS (P < 0.05). Moreover, in the multivariate analysis, N stage still acted as prognostic for DFS (P = 0.019); OS differed significantly in different T stages, chemotherapy selection and serum CEA levels after adjustment (P < 0.05).

Conclusion

Classical driven gene mutations were rare in LCNEC. Tumor N stage appeared as prognostic for DFS, while serum positive CEA, different adjuvant chemotherapy strategies, and T stage were independent prognostic factors for OS. Etoposide–platinum regime seemed to be a better choice which should be confirmed by further prospective investigations.
Consolidation Immunotherapy After Platinum-Based Chemoradiotherapy in Patients With Unresectable Stage III Non-Small Cell Lung Cancer—Cross-Sectional Study of Eligibility and Administration Rates
Authors: Eichkorn Tanja , Bozorgmehr Farastuk , Regnery Sebastian , Dinges Lisa A. , Kudak Andreas , Bougatf Nina , Weber Dorothea , Christopoulos Petros , Muley Thomas , Kobinger Sonja , König Laila , Hörner-Rieber Juliane , Adeberg Sebastian , Heussel Claus Peter , Thomas Michael , Debus Jürgen , El Shafie Rami A.
Published: December 2020

Introduction

The PACIFC trial demonstrated a significant benefit of durvalumab consolidation immunotherapy (CIT) after definitive platinum-based chemoradiotherapy (P-CRT) for survival in stage III non-small cell lung cancer (NSCLC). It is unknown how many patients are eligible in clinical practice to receive CIT according to PACIFIC criteria compared to real administration rates and what influencing factors are.

Patients and Methods

We analyzed 442 patients with unresectable stage III NSCLC who received P-CRT between 2009 and 2019 regarding CIT eligibility rates according to PACIFIC criteria and administration rates since drug approval.

Results

Sixty-four percent of 437 patients were male, median age was 63 years [interquartile range (IQR): 57–69]. The most common histologic subtypes were adenocarcinoma (42.8%) and squamous cell carcinoma (41.1%), most tumors were in stage IIIB (56.8%). Mean PD-L1 tumor proportion score (TPS) was 29.8% (IQR: 1–60). The median total RT dose was 60 Gy (IQR: 60–66). Platinum component of P-CRT was evenly distributed between cisplatin (51.4%) and carboplatin (48.6%). 50.3% of patients were eligible for CIT according to PACIFIC criteria. Observed contraindications were progressive disease according to RECIST (32.4%), followed by a PD-L1 TPS < 1% (22.3%), pneumonitis CTCAE ≥ 2 (12.6%) and others (4.9%). One year after drug approval, 85.6% of patients who were eligible according to PACIFIC criteria actually received CIT. Time interval between chemotherapy start and radiation therapy start (OR 0.9, 95% CI: [0.9; 1.0] p = 0.009) and probably cisplatin as platinum-component of P-CRT (OR 1.5, 95% CI: [1.0; 2.4] p < 0.061) influence CIT eligibility. Highly positive PD-L1 TPS (≥50%; (OR 2.4, 95% CI: [1.3; 4.5] p = 0.004) was associated to a better chance for CIT eligibility.

Conclusion

Eighty-five percent of potentially eligible patients received CIT one year after drug approval. Fifty percent of patients did not meet PACIFIC criteria for durvalumab eligibility, this was mainly caused by disease progression during platinum-based CRT, followed by therapy-related pneumonitis and PD-L1 TPS < 1% (in view of the EMA drug approval).
Salient Conclusive Remarks on Epidemiology and Clinical Manifestations of Pediatric COVID-19: Narrative Review
Authors: Ali Abdelwahid Saeed , Al-Hakami Ahmed Mossa , Shati Ayed Abdullah , Asseri Ali Alsuheel , Al-Qahatani Saleh Mohammed
Published: December 2020

The ongoing pandemic of COVID-19, which is caused by the novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), constituted significant public health concerns and impacted the human populations with massive economic and social burdens worldwide. The disease is known to infect people of all ages, including children, adults, and the elderly. Although several reports about pediatric COVID-19 were seen in the literature, we believe that the epidemiology and pathology of the infection described in these reports are not conclusive. Therefore, in this scientific communication, a narrative review study was performed to shed some light on the characteristic epidemiological features and clinical phenotypes of pediatric COVID-19. In this report, we had compiled and presented the different epidemiological features of the disease related to the age of infection, virus acquisition, explanations of the low infectivity rates, and consequences of infections. The discriminatory clinical manifestations of the disease in children were also addressed and discussed in this review. The search included the data published from the date of the start of the pandemic in December 2019 up to October 2020. Our literature search revealed that children of all ages, including neonates, had been infected by the virus. Despite the fact that pediatric COVID-19 is less common to occur, as compared to the disease in adults, the infected children usually manifest the disease symptomatology in benign form. Asymptomatic and symptomatic adult patients are the primary source of the virus to the children. Intrauterine transmission of the virus and breastfeeding infections to the neonates were hypothesized in some studies but ruled out since they were not confirmed. Intensive review and discussion warranting the low infection rates and benign conditions of COVID-19 in children were also made in this study. As documented in many studies, the infectivity, morbidity, and mortality rates of the disease among the children populations are much lower than those in adults. They also seem to be lower than those observed during SARS-CoV and MERS-CoV epidemics. The described clinical phenotypes of COVID-19 in children do not differ much from those of adults, and complications of the disease seem to be associated with comorbidities.
The Increased Expression of an Engrailed to Sustain Shell Formation in Response to Ocean Acidification
Authors: Zhang Yukun , Liu Zhaoqun , Zong Yanan , Zheng Yan , Li Yinan , Han Zirong , Wang Lingling , Song Linsheng
Published: December 2020

Engrailed is a transcription factor required in numerous species for important developmental steps such as neurogenesis, segment formation, preblastoderm organization, and compartment formation. Recent study has proved that engrailed is also a key gene related to shell formation in marine bivalves. In the present study, the expression pattern of an engrailed gene (Cgengrailed-1) in Pacific oysterCrassostrea gigasunder CO2-driven acidification was investigated to understand its possible role in the regulation of shell formation and adaptation to ocean acidification (OA). The open reading frame (ORF) ofCgengrailed-1 was obtained, which was of 690 bp encoding a polypeptide of 229 amino acids with a HOX domain. Phylogenetic analysis indicated that the deduced amino acid sequence ofCgengrailed-1 shared high homology with other engraileds fromDrosophila melanogaster,Mizuhopecten yessoensi, andCrassostrea virginica. The mRNA transcripts ofCgengrailed-1 were constitutively expressed in various tissues with the highest expression levels detected in labial palp and mantle, which were 86.83-fold (p< 0.05) and 75.87-fold (p< 0.05) higher than that in hepatopancreas. The mRNA expression ofCgengrailed-1 in mantle decreased dramatically after moderate (pH 7.8) and severe (pH 7.4) acidification treatment (0.75- and 0.15-fold of that in control group,p< 0.05). The results of immunofluorescence assay demonstrated that the expression level ofCgengrailed-1 in the middle fold of mantle increased significantly upon moderate and severe acidification treatment. Moreover, after the oyster larvae received acidification treatment at trochophore stage, the mRNA expression levels ofCgengrailed-1 increased significantly in D-shape larvae stages, which was 3.11- (pH 7.8) and 4.39-fold (pH 7.4) of that in control group (p< 0.05). The whole-mount immunofluorescence assay showed thatCgengrailed-1 was mainly expressed on the margin of shell gland, and the periostracum in trochophore, early D-shape larvae and D-shape larvae in both control and acidification treatment groups, and the intensity of positive signals in early D-shape larvae and D-shape larvae increased dramatically under acidification treatment. These results collectively suggested that the expression ofCgengrailed-1 could be triggered by CO2-driven acidification treatment, which might contribute to induce the initial shell formation in oyster larvae and the formation of periostracum in adult oyster to adapt to the acidifying marine environment.
Senescent Cell Depletion Through Targeting BCL-Family Proteins and Mitochondria
Authors: Fan Ying , Cheng Jiaoqi , Zeng Huihong , Shao Lijian
Published: December 2020

Senescent cells with replicative arrest can be generated during genotoxic, oxidative, and oncogenic stress. Long-term retention of senescent cells in the body, which is attributed to highly expressed BCL-family proteins, chronically damages tissues mainly through a senescence-associated secretory phenotype (SASP). It has been documented that accumulation of senescent cells contributes to chronic diseases and aging-related diseases. Despite the fact that no unique marker is available to identify senescent cells, increased p16INK4a expression has long been used as an in vitro and in vivo marker of senescent cells. We reviewed five existing p16INK4a reporter mouse models to detect, isolate, and deplete senescent cells. Senescent cells express high levels of anti-apoptotic and pro-apoptotic genes compared to normal cells. Thus, disrupting the balance between anti-apoptotic and pro-apoptotic gene expression, such as ABT-263 and ABT-737, can activate the apoptotic signaling pathway and remove senescent cells. Mitochondrial abnormalities in senescent cells were also discussed, for example mitochondrial DNA mutation accumulation, dysfunctional mitophagy, and mitochondrial unfolded protein response (mtUPR). The mitochondrial-targeted tamoxifen, MitoTam, can efficiently remove senescent cells due to its inhibition of respiratory complex I and low expression of adenine nucleotide translocase-2 (ANT2) in senescent cells. Therefore, senescent cells can be removed by various strategies, which delays chronic and aging-related diseases and enhances lifespan and healthy conditions in the body.
Two Splice Isoforms of Leptinotarsa Ecdysis Triggering Hormone Receptor Have Distinct Roles in Larva-Pupa Transition
Authors: Shen Chen-Hui , Xu Qing-Yu , Fu Kai-Yun , Guo Wen-Chao , Jin Lin , Li Guo-Qing
Published: December 2020

Insect ecdysis triggering hormone (ETH) receptors (ETHRs) are rhodopsin-like G protein-coupled receptors. Upon binding its ligand ETH, ETHR initiates a precisely programed ecdysis behavior series and physiological events. InDrosophila melanogaster, theethrgene produces two functionally distinct splicing isoforms,ethraandethrb. ETH/ETHRA activates eclosion hormone (EH), kinin, crustacean cardioactive peptide (CCAP), and bursicon (burs and pburs) neurons, among others, in a rigid order, to elicit the behavioral sequences and physiological actions for ecdysis at all developmental stages, whereas ETH/ETHRB is required at both pupal and adult ecdysis. However, the role of ETHRB in regulation of molting has not been clarified in any non-drosophila insects. In the present paper, we found that 20-hydroxyecdysone (20E) signaling triggers the expression of bothethraandethrbin a Coleopteran insect pest, the Colorado potato beetleLeptinotarsa decemlineata. RNA interference (RNAi) was performed using double-stranded RNAs (dsRNAs) targeting the common (dsethr) or isoform-specific (dsethra, dsethrb) regions ofethr. RNAi of dsethr, dsethra, or dsethrbby the final-instar larvae arrested larva development. The arrest was not rescued by feeding 20E. All theethradepleted larvae stopped development at prepupae stage; the body cavity was expanded by a large amount of liquid. Comparably, more than 80% of theethrbRNAi larvae developmentally halted at the prepupae stage. The remainingLdethrbhypomorphs became pupae, with blackened wings and highly-expressedburs,pbursand four melanin biosynthesis genes. Therefore, ETHRA and ETHRB play isoform-specific roles in regulation of ecdysis during larva-pupa transition inL. decemlineata.
Comparison of Psychological Stress Levels and Associated Factors Among Healthcare Workers, Frontline Workers, and the General Public During the Novel Coronavirus Pandemic
Authors: Luan Rongrong , Pu Weidan , Dai Lilei , Yang Rui , Wang Peng
Published: December 2020

Objective: We aimed to conduct a comparative analysis of the psychological stress experienced by healthcare workers, frontline workers, and the general public and to assess the factors associated with psychological stress in each of these groups.

Methods: We conducted an online survey targeting healthcare workers, frontline workers, and the general public. Psychological stress was assessed with the revised impact of event scale (IES-R). Univariable and multivariable logistic regression analyses were conducted.

Results: We surveyed 1,336 participants (64.6% female; mean age, 36.6). The occupation group distribution of respondents was 50.7% healthcare workers, 27.2% frontline workers, and 22.1% general public. The healthcare (23.6 ± 15.8) and frontline (23.6 ± 17.8) workers had higher IES-R scores than the general public (15.3 ± 10.6; p < 0.01). Poor health perception and perception of infection avoidance were associated with psychological stress in the healthcare and frontline workers, but not in the general public.

Conclusion: Both healthcare and frontline workers are suffering elevated psychological stress, compared to the general public, and this elevated stress may be related especially to their perceptions of their own health and infection risk. Interventions addressing these factors should be developed to alleviate psychological stress in these populations, and thus reduce their risk of mental illness pathogenesis.
Interprofessional Education: Reaching Health Professionals With an Interactive Professional Virtual/Online Event on Advocacy and Policy
Authors: Liller Karen D. , Pruitt Zachary , Burke Somer Goad
Published: December 2020

Competencies in health policy and advocacy should be developed by all health professionals to effectively advance their professions but also effectively collaborate in interprofessional teams to improve public health. However, the COVID-19 epidemic presents a challenge to reaching students of health professions through face-to-face offerings. To meet this need, the University of South Florida College of Public Health developed asynchronous and synchronous online health policy and advocacy modules delivered to an interprofessional group of students pursuing health careers. After learning policy and advocacy material individually through a self-paced online curriculum, faculty gathered the students for a synchronous online event where they formed collaborative groups. In interprofessional teams, students prepared and presented advocacy briefs that were critiqued by the faculty. Post-event evaluation results showed that most students strongly agreed that the interprofessional event was very effective, and they all would recommend the program to other students. Universities and colleges educating students of health professions can take advantage of the technologies employed to keep students safe in the COVID-19 pandemic and still reach students effectively with interprofessional health policy and advocacy content.
Field Evaluation of the Interferon Gamma Assay for Diagnosis of Tuberculosis in Water Buffalo (Bubalus bubalis) Comparing Four Interpretative Criteria
Authors: Martucciello Alessandra , Vitale Nicoletta , Mazzone Piera , Dondo Alessandro , Archetti Ivonne , Chiavacci Laura , Cerrone Anna , Gamberale Fabrizio , Schiavo Lorena , Pacciarini Maria Lodovica , Boniotti Maria Beatrice , De Carlo Esterina
Published: December 2020

Bovine tuberculosis (bTB) is a worldwide zoonosis that affects many species of domestic and wild animals. Mycobaterium bovis is the main cause of infection in water buffalo (Bubalus bubalis) and bovines and is of great concern for human health and for buffalo producers in Italy. The bTB eradication programme is based on slaughterhouse surveillance and intradermal skin tests. Other in vivo diagnostic methods such as the interferon-gamma (IFN-γ) assay have been developed and are widely used in cattle to accelerate the elimination of bTB positive animals. The present study is the first to assess the use and performance of IFN-γ assays, which is used as an ancillary test for bTB diagnosis in water buffalo, and presents the results of a field-evaluation of the assay from 2012 to 2019 during the buffalo bTB eradication programme in Italy. The study involved 489 buffaloes with a positive result to the single intradermal tuberculin test (SITT). The IFN-γ assays and single intradermal comparative tuberculin test were used as confirmation tests. Then, a total of 458 buffaloes, reared on officially tuberculosis-free (OTF) herds, that were confirmed bTB-free for at least the last 6 years were subjected to IFN-γ testing. Furthermore, to evaluate the IFN-γ test in an OTF herd with Paratuberculosis (PTB) infection, 103 buffaloes were subjected to SITT and IFN-γ test simultaneously. Four interpretative criteria were used, and the IFN-γ test showed high levels of accuracy, with sensitivity levels between 75.3% (CI 95% 71.2–79.0%) and 98.4% (CI 95% 96.7–99.4%) and specificity levels between 94.3% (CI 95% 91.2–96.50%) and 98.5% (CI 95% 96.9–99.4%), depending on the criterion used. Finally, in the OTF herd with PTB infection, in buffalo, the IFN-γ test displayed high specificity values according to all 4 interpretative criteria, with specificity levels between 96.7% (CI 95% 88.4–99.5%) and 100% (CI 95% 96.2–100%), while SITT specificity proved unsatisfactory, with a level of 45.3% (CI 95% 35.0–55.7%). Our results showed that the IFN-γ test in the buffalo species could reach high Sensitivity and Specificity values, and that the level of Sensitivity and Specificity could be chosen based on the interpretative criterion and the antigens used depending on the health status of the herd and the epidemiological context of the territory. The IFN-γ test and the use of different interpretative criteria proved to be useful to implement bTB diagnostic strategies in buffalo herds, with the possibility of a flexible use of the assay.
Butaphosphan and Cyanocobalamin Supplementation in Semen Extender on Chilled Boar Sperm Quality and Life Span
Authors: Suwimonteerabutr J. , Chumsri S. , Tummaruk P. , Nuntapaitoon Morakot
Published: December 2020

The objective of the present study was to determine the effect of butaphosphan and cyanocobalamin supplementation in semen extender on chilled boar sperm quality and life span. A total of 35 ejaculates of boar semen were included. The semen was diluted with Beltsville thawing solution extender supplemented with different concentrations of butaphosphan and cyanocobalamin [0 (control), 0.1, 0.2, 0.3, 0.4, and 0.5%] in the diluted semen. The semen samples were evaluated using a computer-assisted sperm analysis system to determine sperm motility and sperm kinetic parameters (i.e., the curvilinear velocity, VCL; straight line velocity, VSL; average path velocity, VAP; linearity, LIN; straightness, STR; amplitude of lateral head, ALH; wobble, WOB; and beat cross frequency, BCF). Additionally, sperm viability, acrosome integrity, mitochondrial activity, and plasma membrane integrity were evaluated after 4 (day 0), 72 (day 3), 120 (day 5), and 168 (day 7) h of storage using SYBR-14–ethidium homodimer-1 (EthD-1), EthD-1, JC-1, and the short hypo-osmotic swelling test, respectively. The analyses were carried out by using the general linear mixed model (MIXED) procedure of SAS. The statistical models for each data set included group, day after storage, and interaction between group and day after storage. The boar was included as a random effect. On day 0 after storage, progressive motility, VCL, VSL, VAP, and plasma membrane integrity of boar sperm in 0.3% of butaphosphan and cyanocobalamin supplementation were greater than those in the 0.4 and 0.5% groups (P< 0.05). On day 3 after storage, total motility and progressive motility, VCL, VSL, VAP, LIN, WOB, BCF, and plasma membrane integrity in 0.3% of butaphosphan and cyanocobalamin supplementation were significantly greater than those in the control group (P< 0.05). The total motility and progressive motility, VAP, and WOB in 0.3% of butaphosphan and cyanocobalamin supplementation were greater than those in the control group on day 5 after storage (P< 0.05). No effects of butaphosphan and cyanocobalamin supplementation on acrosome integrity and mitochondria activity were found on days 3, 5, and 7 after storage. However, the motility and progressive motility and the values for all sperm kinetic parameters except ALH in 0.3% of butaphosphan and cyanocobalamin supplementation were greater than those in the control group on day 7 after storage (P< 0.05). In conclusion, 0.3% of butaphosphan and cyanocobalamin supplementation in semen extender improved sperm motility, sperm activity, morphology, and life span in chilled boar sperm.
Effects of Pre-Calving Body Condition and Different post partum Concentrate Feed Proportions on Immune-Associated and Hematological Parameters in Pluriparous Dairy Cows
Authors: Bünemann Katharina , Frahm Jana , Kersten Susanne , Hüther Liane , Meyer Ulrich , Sauerwein Helga , Hummel Jürgen , Zeyner Annette , Dänicke Sven
Published: December 2020

The present study aimed at evaluating the influences of different concentrate feed proportions in the ration offered to dairy cows post partum with different body condition scores (BCS) before calving. Therefore, 60 pluriparous cows were divided 42 days before expected calving into two groups with a higher or an adequate BCS. After calving, both groups were further subdivided into a group fed a ration with either a low concentrate feed proportion (C, 35% at dry matter basis) or a high (60% at dry matter basis) one. It was hypothesized that different BCS would lead to different reactions concerning varying concentrate feed proportions. Isolated BCS effects were detected in the white blood profile only before calving. Neither low nor high concentrate feed proportions affected hematological, blood immune cell phenotypes and inflammatory markers consistently irrespective of BCS group. It was concluded, that the assessed BCS span covered a range in which the capability of cows to cope with different dietary post partum energy supply remained unchanged.
Slow Blink Eye Closure in Shelter Cats Is Related to Quicker Adoption
Authors: Humphrey Tasmin , Stringer Faye , Proops Leanne , McComb Karen
Published: December 2020

The process of domestication is likely to have led to the development of adaptive interspecific social abilities in animals. Such abilities are particularly interesting in less gregarious animals, such as cats. One notable social behaviour that cats exhibit in relation to humans is the slow blink sequence, which our previous research suggests can function as a form of positive communication between cats and humans. This behaviour involves the production of successive half blinks followed by either a prolonged narrowing of the eye or an eye closure. The present study investigates how cat (n = 18) slow blink sequences might affect human preferences during the adoption of shelter cats. Our study specifically tested (1) whether cats’ propensity to respond to human-initiated slow blinking was associated with their speed of rehoming from a shelter environment, and (2) whether cats’ anxiety around humans was related to their tendency to slow blink. Our experiments demonstrated that cats that showed an increased number of and longer eye closures in response to human slow blinks were rehomed faster, and that nervous cats, who had been identified as needing desensitisation to humans, tended to spend more time producing slow blink sequences in response to human slow blinks than a non-desensitisation group. Collectively, these results suggest that the cat slow blink sequence is perceived as positive by humans and may have a dual function—occurring in both affiliative and submissive contexts.
Antibacterial and Antifungal Properties of Composite Polyethylene Materials Reinforced with Neem and Turmeric
Authors: Sunthar Thefye P. M. , Marin Elia , Boschetto Francesco , Zanocco Matteo , Sunahara Hirofumi , Ramful Raviduth , Kamei Kaeko , Zhu Wenliang , Pezzotti Giuseppe
Published: December 2020

With the increased scientific interest in green technologies, many researches have been focused on the production of polymeric composites containing naturally occurring reinforcing particles. Apart from increasing mechanical properties, these additions can have a wide range of interesting effects, such as increasing the resistance to bacterial and fungal colonization. In this work, different amounts of two different natural products, namely neem and turmeric, were added to polyethylene to act as a natural antibacterial and antifungal product for food packaging applications. Microscopic and spectroscopic characterization showed that fractions of up to 5% of these products could be dispersed into low-molecular weight polyethylene, while higher amounts could not be properly dispersed and resulted in an inhomogeneous, fragile composite. In vitro testing conducted with Escherichia coli, Staphylococcus aureus, and Candida albicans showed a reduced proliferation of pathogens when compared to the polyethylene references. In particular, turmeric resulted in being more effective against E. coli when compared to neem, while they had similar performances against S. aureus. Against C. albicans, only neem was able to show a good antifungal behavior, at high concentrations. Tensile testing showed that the addition of reinforcing particles reduced the mechanical properties of polyethylene, and in the case of turmeric, it was further reduced by UV irradiation.
Histone Carbonylation Is a Redox-Regulated Epigenomic Mark That Accumulates with Obesity and Aging
Authors: Hauck Amy K. , Zhou Tong , Upadhyay Ambuj , Sun Yuxiang , O’Connor Michael B. , Chen Yue , Bernlohr David A.
Published: December 2020

Oxidative stress is a hallmark of metabolic disease, though the mechanisms that define this link are not fully understood. Irreversible modification of proteins by reactive lipid aldehydes (protein carbonylation) is a major consequence of oxidative stress in adipose tissue and the substrates and specificity of this modification are largely unexplored. Here we show that histones are avidly modified by 4-hydroxynonenal (4-HNE) in vitro and in vivo. Carbonylation of histones by 4-HNE increased with age in male flies and visceral fat depots of mice and was potentiated in genetic (ob/ob) and high-fat feeding models of obesity. Proteomic evaluation of in vitro 4-HNE- modified histones led to the identification of both Michael and Schiff base adducts. In contrast, mapping of sites in vivo from obese mice exclusively revealed Michael adducts. In total, we identified 11 sites of 4-hydroxy hexenal (4-HHE) and 10 sites of 4-HNE histone modification in visceral adipose tissue. In summary, these results characterize adipose histone carbonylation as a redox-linked epigenomic mark associated with metabolic disease and aging.
From Light to Displacement: A Design Framework for Optimising Spectral-Domain Low-Coherence Interferometric Sensors for In Situ Measurement
Authors: Hovell Tom , Petzing Jon , Justham Laura , Kinnell Peter
Published: December 2020

Growing requirements for in situ metrology during manufacturing have led to an increased interest in optical coherence tomography (OCT) configurations of low coherence interferometry (LCI) for industrial domains. This paper investigates the optimisation of spectral domain OCT hardware and signal processing for such implementations. A collation of the underlying theory of OCT configured LCI systems from disparate sources linking the journey of the light reflected from the object surface to the definition of the measurand is presented. This is portrayed in an applicable, comprehensible design framework through its application to profilometry measurements for optimising system performance.
Biomechanical Comparison of Different Volar Screw Placements for Horizontal Oblique Scaphoid Fractures
Authors: Lin Ting-Sheng , Ma Ching-Hou , Wu Chin-Hsien , Yen Cheng-Yo , Jou I-Ming , Tu Yuan-Kun
Published: December 2020

Recently, some surgeons reported that most scaphoid waist fractures were horizontal oblique and not transverse in orientation. Therefore, this cadaveric study aimed to biomechanically compare fixation strength between central and eccentric screw placements for the volar fixation of this most common scaphoid waist fracture. Eight matched pairs of fresh-frozen forearm cadaver specimens were prepared for testing and randomly assigned to two groups: group I specimens were fixed by screws in a central placement, and group II specimens were fixed by screws in an eccentric placement. Horizontal oblique osteotomy was performed along the scaphoid waist. Then, each specimen was placed under the increasing load of a pneumatically driven plunger. We recorded stiffness, load to failure, and failure mechanisms between the central and eccentric screw placement groups. Stiffness was higher in central screw placement (74.1 N/mm) than in eccentric screw placement (29.39 N/mm). The median loads to failure in groups I and II were 54.14 and 26.22 N, respectively. In this biomechanical model, we demonstrated that central screw placement is superior to eccentric placement in terms of fixation strength. However, further clinical investigation is warranted to evaluate whether the different screw placements for volar approach of horizontal oblique scaphoid fractures affect the clinical outcomes.
The Role of Chitosan and Graphene Oxide in Bioactive and Antibacterial Properties of Acrylic Bone Cements
Authors: Zapata Mayra Eliana Valencia , Tovar Carlos David Grande , Hernandez José Herminsul Mina
Published: December 2020

Acrylic bone cements (ABC) are widely used in orthopedics for joint fixation, antibiotic release, and bone defect filling, among others. However, most commercially available ABCs exhibit a lack of bioactivity and are susceptible to infection after implantation. These disadvantages generate long-term loosening of the prosthesis, high morbidity, and prolonged and expensive treatments. Due to the great importance of acrylic bone cements in orthopedics, the scientific community has advanced several efforts to develop bioactive ABCs with antibacterial activity through several strategies, including the use of biodegradable materials such as chitosan (CS) and nanostructures such as graphene oxide (GO), with promising results. This paper reviews several studies reporting advantages in bioactivity and antibacterial properties after incorporating CS and GO in bone cements. Detailed information on the possible mechanisms by which these fillers confer bioactive and antibacterial properties to cements, resulting in formulations with great potential for use in orthopedics, are also a focus in the manuscript. To the best of our knowledge, this is the first systematic review that presents the improvement in biological properties with CS and GO addition in cements that we believe will contribute to the biomedical field.
Influence of Obesity and Exercise on β2-Adrenergic-Mediated Anti-Inflammatory Effects in Peritoneal Murine Macrophages
Authors: Martín-Cordero Leticia , Gálvez Isabel , Hinchado María Dolores , Ortega Eduardo
Published: December 2020

Obesity is a chronic low-grade inflammatory condition, and β2-adrenergic agonists as well as exercise have been proposed as anti-inflammatory strategies in obesity, so it is critical to accurately determine the effects of β2-adrenergic stimulation, especially when combined with other non-pharmacological therapies. The aim of this investigation was to determine the effect of β2-adrenergic activation on the inflammatory profile and phenotype of macrophages, and whether these effects could be affected by obesity and exercise in this condition. High-fat diet-induced obese and lean C57BL/6J mice were allocated to sedentary or exercised groups. The inflammatory profiles and phenotypes of their peritoneal macrophages were assessed by flow cytometry in the presence or absence of the selective β2-adrenergic receptor agonist terbutaline. β2-adrenergic activation caused global phenotypic anti-inflammatory effects in lean and obese sedentary mice, which were more drastic (also including anti-inflammatory effects on the cytokine profile) in obese animals. In exercised lean and obese animals, this anti-inflammatory effect is weaker and only evident by decreased iNOS and IL-8 expression, without changes in the anti-inflammatory markers. Therefore, β2-adrenergic activation leads to anti-inflammatory effects, but these effects are modulated by obesity in sedentary conditions, as well as by regular exercise; but not by obesity in trained conditions.
Conformational Landscapes of Halohydrin Dehalogenases and Their Accessible Active Site Tunnels
Authors: Estévez-Gay Miquel , Iglesias-Fernández Javier , Osuna Sílvia
Published: December 2020

Halohydrin dehalogenases (HHDH) are industrially relevant biocatalysts exhibiting a promiscuous epoxide-ring opening reactivity in the presence of small nucleophiles, thus giving access to novel carbon–carbon, carbon–oxygen, carbon–nitrogen, and carbon–sulfur bonds. Recently, the repertoire of HHDH has been expanded, providing access to some novel HHDH subclasses exhibiting a broader epoxide substrate scope. In this work, we develop a computational approach based on the application of linear and non-linear dimensionality reduction techniques to long time-scale Molecular Dynamics (MD) simulations to study the HHDH conformational landscapes. We couple the analysis of the conformational landscapes to CAVER calculations to assess their impact on the active site tunnels and potential ability towards bulky epoxide ring opening reaction. Our study indicates that the analyzed HHDHs subclasses share a common breathing motion of the halide binding pocket, but present large deviations in the loops adjacent to the active site pocket and N-terminal regions. Such conformational differences affect the available tunnels for epoxide binding to the active site. The superior activity of the HHDH G subclass towards bulkier substrates is explained by the additional structural elements delimiting the active site region, its rich conformational heterogeneity, and the substantially wider and frequently observed active site tunnels. This study therefore provides key information for HHDH promiscuity and engineering.
Broad and Complex Roles of NBR1-Mediated Selective Autophagy in Plant Stress Responses
Authors: Zhang Yan , Chen Zhixiang
Published: December 2020

Selective autophagy is a highly regulated degradation pathway for the removal of specific damaged or unwanted cellular components and organelles such as protein aggregates. Cargo selectivity in selective autophagy relies on the action of cargo receptors and adaptors. In mammalian cells, two structurally related proteins p62 and NBR1 act as cargo receptors for selective autophagy of ubiquitinated proteins including aggregation-prone proteins in aggrephagy. Plant NBR1 is the structural and functional homolog of mammalian p62 and NBR1. Since its first reports almost ten years ago, plant NBR1 has been well established to function as a cargo receptor for selective autophagy of stress-induced protein aggregates and play an important role in plant responses to a broad spectrum of stress conditions including heat, salt and drought. Over the past several years, important progress has been made in the discovery of specific cargo proteins of plant NBR1 and their roles in the regulation of plant heat stress memory, plant-viral interaction and special protein secretion. There is also new evidence for a possible role of NBR1 in stress-induced pexophagy, sulfur nutrient responses and abscisic acid signaling. In this review, we summarize these progresses and discuss the potential significance of NBR1-mediated selective autophagy in broad plant responses to both biotic and abiotic stresses.
Filamin A Orchestrates Cytoskeletal Structure, Cell Migration and Stem Cell Characteristics in Human Seminoma TCam-2 Cells
Authors: Welter Harald , Herrmann Carola , Fröhlich Thomas , Flenkenthaler Florian , Eubler Katja , Schorle Hubert , Nettersheim Daniel , Mayerhofer Artur , Müller-Taubenberger Annette
Published: December 2020

Filamins are large dimeric F-actin cross-linking proteins, crucial for the mechanosensitive properties of a number of cell types. Due to their interaction with a variety of different proteins, they exert important regulatory functions. However, in the human testis the role of filamins has been insufficiently explored. Immunohistochemical staining of human testis samples identified filamin A (FLNA) in spermatogonia and peritubular myoid cells. Investigation of different testicular tumor samples indicated that seminoma also express FLNA. Moreover, mass spectrometric analyses identified FLNA as one of the most abundant proteins in human seminoma TCam-2 cells. We therefore focused on FLNA in TCam-2 cells, and identified by co-immunoprecipitation LAD1, RUVBL1 and DAZAP1, in addition to several cytoskeletal proteins, as interactors of FLNA. To study the role of FLNA in TCam-2 cells, we generated FLNA-deficient cells using the CRISPR/Cas9 system. Loss of FLNA causes an irregular arrangement of the actin cytoskeleton and mechanical instability, impaired adhesive properties and disturbed migratory behavior. Furthermore, transcriptional activity of typical stem cell factors is increased in the absence of FLNA. In summary, our data suggest that FLNA is crucially involved in balancing stem cell characteristics and invasive properties in human seminoma cells and possibly human testicular germ cells.