bluuebunny/crossref_metadata_2025 huggingface dataset:
Following a dietary pattern based on Dietary Guidelines for Americans may lead to reduced preference for sweet taste
Authors: Lee Fanny , Kishimura Kathleen , Horn William , Ilyas Amar , Que Excel , Hall Joanne , Welch Lucas , Krishnan Sridevi , Keim Nancy L
Published: June 2021

Objective

Dietary intake of added sugars in the United States is significantly higher than what is recommended by the Dietary Guidelines for Americans (DGA) and by other health organizations. There is limited research on how reducing the intake of added sugars would affect or change taste perception related to sugar. Our objective was to determine if sweet taste threshold and sweet preference changes in response to a diet intervention based on the recommendations in the 2010 DGA compared to an intervention based on the typical American diet (TAD) as described by recent surveys of U.S. adults.

Methods

Data for this report is from an eight‐week controlled feeding trial. Overweight or obese women, with insulin resistance and/or dyslipidemia, aged 20–65 years were randomized into one of two diet groups: the DGA diet or the TAD. Detection taste threshold was determined using a three‐alternative‐forced choice method and sweet preference was measured using the Monell forced‐choice, paired‐comparison tracking procedure. Measurements were obtained prior to the dietary intervention at baseline (BL), and after the diet intervention (ADI) to evaluate changes in taste acuity and hedonic preference. Data were log transformed, and analysis of covariance was used to identify differences between the two diet groups. In addition, the change in acuity and hedonic preference was calculated as ADI‐BL. Wilcoxon's rank test was used to identify differences in these parameters between the two groups. This is an on‐going study, with more participant cohorts being added to reach n = 44.

Results

Preliminary results were generated for the first 16 women (Age: DGA ‐ 45.0, TAD‐42.5 y; BMI: DGA – 30.4, TAD – 33.0 kg/m2) who have completed the study. Usual energy intake (kcals), and percent‐added sugars or sweet‐food intake were not different at BL between DGA and TAD (p = 0.92, 0.63, 0.92, respectively). There was no significant difference (p > 0.05) between diets in the change in sweet threshold or sweet preference. The DGA intervention, however, resulted in a larger reduction in the level of preferred sweetness compared to the TAD diet, when controlling for BL preference (p = 0.03).

Conclusions

Consuming a diet following the DGA may possibly lower preference for sweet foods when compared to a TAD. Further, data from the complete cohort will be used to add to this report upon study completion.

Support or Funding Information

Funded by National Dairy Council and USDA, ARS CRIS project #2032 51530 022 00D
Coconut oil prevents hepatic steatitis but not adipose inflammation in obese mice
Authors: Picklo Matthew , Idso Joseph , Zeng Huawei
Published: June 2021

While saturated fat intake is associated with obesity and its comorbidities, there are little data indicating the impact of specific saturated fatty acids (SFA).In particular, data are lacking in which only SFA type, but not other fatty acids, is changed. In this work, we tested the hypothesis that intake of obesogenicdiets containing medium chain SFA reduce hepatic steatosis and insulin resistance. Male, C57BL/6J mice were fedobesogenic diets of 48% energy (en) fat (28 % SFA, 14% oleic acid, and 6% polyunsaturated fatty acid) or a control diet with 16% en fat (5% SFA, 4% oleicacid, and 7% PUFA) for 16 weeks. Obesogenic groups were divided by SFA source:coconut oil‐based (CCO) with high lauric acid, a palm‐oil based (PO) with palmitic acid and stearic acids, and a MIX group with similar levels of the SFAs.

All mice eating the obesogenic diets became obese compared to the control group. While all obese animals were insulin resistant, PO animals had higher insulin resistance (assessed by HOMA‐IR) than CCO and MIX animals. Hepatic triacylglycerides (TAG) were elevated in the PO and MIX groups, but not the CCO group. The accumulation of hepatic lipid was confirmed with histological analysis. Hepatic expression of the inflammatory cytokine MCP‐1 was elevated by intake of the PO diet, but not the CCO and MIX diets. On the other hand, expression of MCP‐1 and TNF alpha in visceral adipose was elevated by all three obesogenic diets. Hepatic protein levels of stearoyl‐CoA desaturase 1(SCD‐1), fatty acid synthase (FASN), but not acetyl CoA carboxylase 1 (ACC1), were reduced by intake of CcO and PO diets. These data indicate that intake of CCO has selective protective effects against hepatic steatosis but not adipose dysfunction. These data indicate a decrease in de novo lipogenes is induced by the obesogenicdiets and that perturbation of other processes such as VLDL secretion or fatty acid oxidation impact hepatic TAG deposition and are SFA‐type dependent.

Support or Funding Information

This work was supported by U.S. Department of Agriculture through USDA‐ARS project 5450‐51000‐048‐00D.
Manipulation of Curcumin Degradation to Enhance its Stability and Biological Activity
Authors: Sanidad Katherine Zabala , Wang Weicang , Zhu Julia , Nimiya Yoshiki , Du Zheyuan , Sukamtoh Elvira , Zhang Guodong
Published: June 2021

Curcumin, a dietary compound from turmeric, is one of the most promising dietary compounds for cancer prevention and inflammation. However, curcumin rapidly degrades at physiological pH with a half‐life of several minutes, making it difficult to discern whether the cancer preventing and inflammation reducing effects are due to curcumin itself or its degradation products. In order to determine which compounds were most responsible for the observed anti‐cancer and anti‐inflammatory effects, we compared the biological activities of curcumin with a mixture of its stable total degradation products (TDP) and the most abundant stable degradation product, bicyclopentadione (BCP). We compared the effects of these compounds on cell proliferation, cell cycle progression, and apoptosis in MC38 colon cancer cells and lipopolysaccharide (LPS)‐induced inflammatory responses and NF‐kB signaling in RAW 264.7 macrophages. Our results showed that compared with curcumin, both TDP and BCP have dramatically reduced effects on cell proliferation, cell cycle progression and apoptosis in MC38 cells, and reduced effects on inhibition of inflammatory responses and NF‐kB signaling in RAW264.7 cells. These results suggest that the observed effects of curcumin are mainly mediated by curcumin itself, rather than its degradation products. We further showed that co‐addition of redox active antioxidants, which stabilizes curcumin in aqueous buffer, significantly enhanced the biological effects of curcumin in MC38 cells. Together, these results suggest that manipulation of curcumin degradation is a promising strategy to enhance its anti‐cancer and anti‐inflammatory effects.

Support or Funding Information

Armstrong Fund of Science Award from University of Massachusetts Amherst and USDA NIFA 2016‐67017‐24423
ARSENIC EXPOSURE PROMOTES AGGRESSIVE BREAST CANCER PHENOTYPE
Authors: Luelsdorf Andre
Published: June 2021

Environmental arsenic (AS) is a class I human carcinogen with established roles in promoting skin, colon, bladder and kidney cancers. The role of AS as a breast carcinogen is less established although numerous studies have indicated that that in cell culture AS promotes the specification of breast cancer towards phenotypes that are estrogen receptor negative (ERα(−)) which are more lethal as well as more challenging to treat. The molecular mechanism involved remain unknown. Our laboratory found that AS promotes alterations in the metabolism of mitochondria reactive oxygen species (ROS) via inhibiting the tumor suppressor Sirtuin 3 which leads to the accumulation of manganese superoxide dismutase (MnSOD) in an acetylated form (MnSOD‐K68Ac) which activates hypoxia induced factor 2α (HIF2α). The activation of HIF2α is a well‐stablished mechanism os stem cell reprogramming that has also been implicated in metastatic recurrence as well as treatment failure in women with breast cancer. Hence, we propose that chrnic AS exposure is a risk factor for the development of ER(−) breast cancer via a mechanism that involves MnSOD acetylation and mitochondria ROS. In support of this idea, we found that exposure of MCF‐7 (normally ERα+), leads to the accumulation of MnSOD‐K68Ac and ER(−) phenotype. Our results indicate that exposure to AS may be a risk factor for the development of ER(−) tumors which are more aggressive and prone to metastasize.

Support or Funding Information

DOD
Streptomyces wadayamensis MppP: A Novel PLP‐Dependent L‐Arginine Hydroxylase in L‐Enduracididine Biosynthesis
Authors: Han Lanlan , Silvaggi Nicholas
Published: June 2021

The nonproteinogenic amino acid L‐enduracididine (L‐End) is a critical component of the mannopeptimycins, a family of cyclic glycopeptide antibiotics with potent activities against drug‐resistant pathogens like MRSA. Creating derivatives of mannopeptimycin and other L‐End‐containing natural products is hampered by the limited availability of L‐End. We are investigating the L‐End biosynthetic pathway in order to develop an efficient enzymatic or chemo‐enzymatic route to produce this unusual amino acid. Recently, we found that MppP is a PLP‐dependent L‐Arg hydroxylase in L‐End biosynthesis in Streptomyces wadayamensis. It reacts with L‐Arg and dioxygen to yield two products, 2‐ketoarginine and 4‐hydroxy‐2‐ketoarginine in a ratio of ~1.7:1. Surprisingly, 1 equivalent of H2O2 is produced for each equivalent of O2 consumed. In addition, the ratio of O2 consumption to L‐Arg consumption was ~1.4:1, suggesting that one product requires 2 equivalents of O2, and the other only 1 equivalent. We have determined the structures of MppP in four states: the internal aldimine, the external aldimine with the substrate, L‐Arg, the product complex with 4‐hydroxy‐2‐ketoarginine, and the product complex with 2‐ketoarginine. According to the structures, the N‐terminal helix is disordered in the internal aldimine and covers the active site only when the substrate is bound. A glutamate residue in the N‐terminal helix, E15, makes a hydrogen bonding interaction with the carboxylate of the substrate, L‐Arg. This observation prompted us to make three N‐terminal variants of SwMppP: E15A, E15Q, and the truncation mutant, SwMppP23‐276. Steady state kinetics showed that the two point mutants had no effect on kcat or KM,L‐Arg. The truncation mutant, however, showed an approximately 10‐fold increase in KM and a 3‐fold decrease in kcat, which reduced the pseudo‐second order rate constant by almost 25‐fold. Interestingly, although the steady state kinetics (as measured by dioxygen consumption) are indistinguishable for the E15A and E15Q variants, the E15A variant does not produce 4‐hydroxy‐2‐ketoarginine, only the abortive product 2‐ketoarginine. Likewise, the truncation mutant also produced only 2‐ketoarginine. Our structural and kinetic characterization of the wild‐type and variant forms of SwMppP have allowed us to propose a revised model where the oxygen incorporated in the hydroxy‐arginine product is derived from water rather than from dioxygen.

Support or Funding Information

National Science Foundation CHE‐1606842
Results of the Italian Pediatric Orthopedics Society juvenile flexible flatfoot survey: diagnosis and treatment options
Authors: Pavone Vito , Vescio Andrea , Andreacchio Antonio , Memeo Antonio , Gigante Cosimo , Lucenti Ludovico , Farsetti Pasquale , Canavese Federico , Moretti Biagio , Testa Gianluca , De Pellegrin Maurizio
Published: June 2021

The objectives of this study were to collect and analyze current diagnosis and treatment options of symptomatic flexible flatfoot (FFF), as well as to identify treatment expectations, among the members of the Italian Pediatric Orthopedics Society (SITOP). Diagnosis and treatment preferences were recorded according to a web-based survey. The survey was divided into six main sections: (1) general clinical parameters; (2) foot aspects; (3) X-ray angles (or lines); (4) expectations; (5) standard clinical assessment; (6) treatment options. One hundred and ten out of 248 SITOP members answered to the questionnaire. Age (85.5%), pain at the level of the plantar arch or fascia (61.8%), fatigue (59.1%) were the clinical parameters of crucial importance. Heel valgus (85.4%), flexibility (61.8%) and forefoot supination (47.3%) were identified as the most important foot aspects. Ninety-two responders (83.6%) identified the ‘improved ability to walk longer without symptoms or discomfort’ as the principal treatment expectation. Pain evaluated through the visual analog scale (VAS) was considered crucial in 31.8% of cases. All respondents confirmed they also treat patients with FFF surgically; in particular, 97.3% of SITOP affiliates declare to perform arthroereisis followed by lateral column lengthening (29.1%) and medializing calcaneal osteotomy (9.1%). Although in this survey heterogeneous findings for diagnosis and treatment of patients with symptomatic FFF within SITOP members were found, a large preference for age, heel valgus, flexibility as clinical aspects and parameters, as well as nonoperative treatment and arthroereisis, was reported.
Cardiovascular disease prevention in individuals with underlying chronic inflammatory disease
Authors: Weber Brittany , Liao Katherine P. , DiCarli Marcelo , Blankstein Ron
Published: June 2021

Purpose of review

Patients with chronic inflammatory disease have an increased risk of cardiovascular disease. This article reviews the current evidence of cardiovascular prevention in three common systemic inflammatory disorders (SIDs): psoriasis, rheumatoid arthritis, and systemic lupus erythematosus.

Recent findings

General population cardiovascular risk assessment tools currently underestimate cardiovascular risk and disease-specific risk assessment tools are an area of active investigation. A disease-specific cardiovascular risk estimator has not been shown to more accurately predict risk compared with the current guidelines. Rheumatoid arthritis-specific risk estimators have been shown to better predict cardiovascular risk in some cohorts and not others. Systemic lupus erythematosus-specific scores have also been proposed and require further validation, whereas psoriasis is an open area of active investigation. The current role of universal prevention treatment with statin therapy in patients with SID remains unclear. Aggressive risk factor modification and control of disease activity are important interventions to reduce cardiovascular risk.

A comprehensive approach that includes cardiovascular risk factor modification, control of systemic inflammation, and increased patient and physician awareness is needed in cardiovascular prevention of chronic inflammation. Clinical trials are currently underway to test whether disease-specific anti-inflammatory therapies will reduce cardiovascular risk.
Long Anterior Zonules and Angle Closure Disease
Authors: Khurana Mona , Ganesh Nagalekshmi , Jaiswal Ashutosh G. , Vijaya Lingam , George Ronnie J. , Balekudaru Shantha
Published: June 2021

Précis:

Angle closure disease was present in 59.3% of eyes with long anterior zonules (LAZ). The cause is multifactorial including a thick anteriorly positioned crystalline lens, shorter axial length, and increased lens thickness to axial length factor.

Purpose:

To study the profile of eyes with LAZ presenting in a glaucoma clinic in a tertiary eye care centre and understand the pathogenesis of angle closure disease in these eyes.

Methods:

This was a retrospective cross-sectional study.

All patients with LAZ seen from January 2014 to December 2018 were included. Demographic and clinical characteristics were noted. LAZ eyes (177 eyes of 177 patients) were compared with an equal number of age and sex-matched controls. LAZ was defined as radially oriented zonular fibers (both pigmented and nonpigmented), extending central to the normal zonular termination zone on the anterior lens surface >1 mm beyond their usual insertion of 1.42±0.24 mm from the lens equator onto the mid peripheral zone or central to it, as seen on slit-lamp examination, following pupillary dilation by a single examiner. Glaucoma was defined according to the International Society for Geographical and Epidemiological Ophthalmology classification. The following biometric parameters were compared: anterior chamber depth (ACD), axial length (AXL), lens thickness (LT), lens position (LP=ACD+0.5×LT), relative lens position (RLP=LP/AXL); lens thickness to axial length factor (LAF=(LT/AXL)×10). LAZ eyes without angle closure disease were also compared with controls.

Results:

Mean age of patients with LAZ was 64.8±8.1 years. Of these, 63.3% were females. Angle closure disease was present in 59.3% (105/177) patients. Majority of these eyes were primary angle closure suspects (PACS) (53.3%, n=56). Significant differences were found between LAZ eyes and controls for LT (4.8±0.38 mm vs. 4.49±0.40 mm, P<0.0001), ACD (2.68±0.39 mm vs. 3.0±0.32 mm, P<0.0001), AXL (22.37±0.79 mm vs. 22.94±1.1, P<0.0001), LAF (2.14±0.19 vs. 1.96±0.21, P<0.0001), and LP (5.07±0.37 vs. 5.3±0.25, P<0.0001).

Conclusions:

Angle closure was present in more than half the eyes with LAZ. Majority of these eyes were PACS or had primary angle closure. LAZ eyes had a thicker lens, shallow AC, a shorter axial length and an increased LAF as compared with age and sex matched normal controls. The presence of LAZ may be an indicator of increased risk for angle closure.
Expression and methylation status of vascular endothelial growth factor and thrombospondin-1 genes in congenital factor XIII-deficient patients with intracranial hemorrhage
Authors: Noroozi-Aghideh Ali , Kashanikhatib Zahra , Naderi Majid , Dorgalaleh Akbar , Azad Mehdi , Alizadeh Shaban
Published: June 2021

Congenital factor XIII (FXIII) deficiency is one of the rarest bleeding disorders, with an incidence of one per 2 million persons. Intracranial hemorrhage (ICH), a major cause of mortality in FXIII deficiency, is reported to be associated with vascular endothelial growth factor (VEGF) and thrombospondin-1 (TSP-1). Therefore, we investigated the association of VEGF and TSP-1 expression and methylation patterns with ICH in congenital FXIII deficiency patients. This study was conducted on 40 participants with FXIII, 20 of whom experienced ICH (cases), and 20 who did not (controls). Methylation pattern, gene expression, and plasma protein level were assessed using bisulfite sequencing PCR, quantitative real-time PCR, and ELISA. We found a partially methylated pattern for both VEGF and TSP-1 (P > 0.05). VEGF mRNA levels of the case group were significantly higher than those of the control group (P < 0.05), whereas TSP-1 mRNA levels did not show significant upregulation (P > 0.05). Plasma VEGF and TSP-1 concentrations in the case group were higher, but not statistically significant (P > 0.05). Our findings showed no obvious correlation between VEGF or TSP-1 methylation patterns and expression, suggesting that their expression in FXIII deficiency may not solely be controlled by gene methylation.
Short and long-term effectiveness and safety of vedolizumab in treatment-refractory patients with ulcerative colitis and Crohn’s disease – a real-world two-center cohort study
Authors: Attauabi Mohamed , Vind Ida , Pedersen Gitte , Bendtsen Flemming , Seidelin Jakob Benedict , Burisch Johan
Published: June 2021

Objectives

Real-world data about sustained clinical remission (SCR) and treatment optimization with vedolizumab for ulcerative colitis (UC) and Crohn’s disease (CD) are scarce. We aimed to investigate the short and long-term effectiveness and safety of vedolizumab in a real-world cohort in Denmark.

Methods

A retrospective two-center cohort study was conducted between November 2014 and November 2019 with the primary outcomes of clinical remission (CR) at weeks 14, 30, 52 and 104 and SCR defined as CR at week 14 through week 52.

Results

The study included 182 patients (UC: 97, CD: 85), all previously exposed to at least one biological therapy. Rates of CR at weeks 14, 30, 52 and 104 were 36.6, 35.1, 34.0 and 27.8%, respectively, in UC, and 31.7, 30.1, 26.5 and 22.4% in CD. SCR was achieved in 19.6 and 20.0%, respectively. In UC and CD, optional dosing of vedolizumab at week 10 (odds ratio [OR] = 0.23 (95% confidence interval [CI], 0.03–1.17), and OR = 0.68 (95% CI, 0.22–2.04)), as well as increase of frequency (OR = .26 (95% CI, 0.01–2.86), and OR = 0.19 (95% CI, 0.01–1.45)), were not associated with CR at week 52. Furthermore, combination treatment with azathioprine was not associated with long-term outcomes. However, dose intensification of vedolizumab successfully restored CR in 65.2 and 57.1% of patients with UC and CD experiencing loss of response.

Conclusions

Vedolizumab is effective in achieving and restoring short and long-term CR and SCR in patients with treatment-refractory UC and CD. This study emphasizes that supplementary dosing at week 10, and simultaneous treatment with azathioprine, did not improve long-term outcomes.
Brief exposure to warm temperatures reduces intron retention in
Kdm6b
in a species with temperature-dependent sex determination
Authors: Marroquín-Flores Rosario A. , Bowden Rachel M. , Paitz Ryan T.
Published: June 2021

Animals with temperature-dependent sex determination (TSD) respond to thermal cues during early embryonic development to trigger gonadal differentiation. TSD has primarily been studied using constant temperature incubations, where embryos are exposed to constant male- or female-producing temperatures, and these studies have identified genes that display sex-specific expression in response to incubation temperature.
Kdm6b
, a histone demethylase gene, has received specific attention as it is among the initial genes to respond to incubation temperature and is necessary for testis development. Interestingly,
Kdm6b
retains an intron when eggs are incubated at a constant male-producing temperature, but the role of thermal variability in this developmental process is relatively understudied. Species with TSD regularly experience thermal cues that fluctuate between male- and female-producing temperatures throughout development but it is unclear how
Kdm6b
responds to such variable temperatures. In this study, we investigate temperature-sensitive splicing in
Kdm6b
by exposing embryos to male- and female-producing thermal conditions. We show a rapid decrease in levels of the intron retaining transcript of
Kdm6b
upon exposure to female-producing conditions. These results demonstrate that, under ecologically relevant conditions, temperature-sensitive splicing can differentially regulate genes critical to TSD.
Safety and efficacy of antiviral therapy alone or in combination in COVID-19 - a randomized controlled trial (SEV COVID Trial)
Authors:   SEV COVID trial group, Singh Budha O , Moirangthem Bikram , Panda Prasan Kumar , Bahurupi Yogesh Arvind , Saha Sarama , Saini Girraj , Dhar Minakshi , Bairwa Mukesh , Pai Venkatesh Srinivasa , Agarwal Ankit , Sindhwani Girish , Handu Shailendra , Ravikant
Published: June 2021

Background

Definitive antiviral treatment is not available for COVID-19 infection except remdesivir that even with many doubts. Various combination antivirals have been tried.

Methods

A single-center, open-label, parallel-arm, stratified randomized controlled trial evaluated the therapeutic potential of hydroxychloroquine and lopinavir-ritonavir in combination with ribavirin in COVID-19. Enrolled patients in severe category were randomized into three groups: A: standard treatment, B: hydroxychloroquine+ribavirin+standard treatment, or C: lopinavir+ritonavir+ribavirin+standard treatment; while non-severe category into two groups: A: standard treatment or B: hydroxychloroquine+ribavirin. Combination antivirals was given for 10 days and followed for 28 days. The primary endpoints were safety, symptomatic and laboratory recovery of organ dysfunctions, and time to SARS-CoV-2 RT-PCR negative report.

Results

Total 111 patients randomized: 24, 23, and 24 in severe category A, B, and C respectively, and 20 in each non-severe group. Two patients receiving ribavirin experienced drug induced liver injury and another developed QT prolongation after hydroxychloroquine. In the severe category, 47.6%, 55%, and 30.09% in A, B, and C groups respectively showed symptomatic recovery compared to 93.3% and 86.7% in A and B groups respectively in the non-severe category at 72hrs (P>0.05).

Conclusions

The results failed to show statistical superiority of the antiviral combination therapies to that of the standard therapy in both the severe and non-severe categories in symptomatic adult patients of COVID-19. However, results do indicate the benefit of non-standard interventional combination therapy in severe disease. Furthermore, the dose of ribavirin needs to be reconsidered in the Indian population.
Salt-inducible kinase (SIK) inhibition is protective in a mouse model of asthma
Authors: van Gijsel-Bonnello Manuel , Darling Nicola J. , McDonald Laura , Sime Mairi , Clark Jonathan , Mezna Mokdad , Schuettelkopf Alexander , Mackay Craig , Bower Justin , McKinnon Heather , Cohen Philip , Arthur J. Simon C.
Published: June 2021

Interleukin-13 (IL-13) and other Th2 cytokines are important regulators of airway hyper-responsiveness, immune cell infiltration and inflammation in allergic asthma, and are produced when immune cells, such as type 2 innate lymphoid cells (ILC2s) and mast cells, are stimulated with IL-33. Here, we report that the IL-33-dependent secretion of IL-13 from ILC2s is prevented by inhibition of the salt-inducible kinases (SIKs), as we have shown previously in mast cells (Darling NJet al., 2021, J. Biol. Chem. doi: 10.1016/j.jbc.2021.100428). We also report that a new SIK inhibitor with improved pharmacokinetic properties suppresses the recruitment of eosinophils to the lungs and serum immunoglobulin E (IgE) levels in theAlternaria alternata-inducedmodel of allergic asthma. Our results suggest that drugs targeting SIK isoforms may have therapeutic potential for the treatment of asthma.
Treadmill exercise promotes retinal astrocyte plasticity and protects against retinal degeneration
Authors: Bales Katie L. , Chacko Alicia S. , Nickerson John M. , Pardue Machelle T. , Boatright Jeffrey H.
Published: June 2021

Exercise has been shown to be an effective neuroprotective intervention that preserves retinal function and structure in several animal models of retinal degeneration. However, retinal cell morphology and cell types governing exercise-induced retinal neuroprotection remain elusive. Previously, we found that the protective effects of exercise in animal models of retinal disease were accompanied by increased levels of circulating and retinal brain derived neurotrophic factor (BDNF) and required intact signal transduction with its high-affinity receptor, tropomyosin kinase B (TrkB). Studies of neurodegenerative diseases in the brain demonstrate that neurons and astrocytes express BDNF and TrkB. Additionally, astrocytes have been shown to alter their morphology in response to exercise. Here, we have investigated the role of retinal astrocytes as mediators of exercise-induced retinal neuroprotection in a light-induced retinal degeneration mouse model (LIRD). We found that treadmill exercise in both our dim (control maintenance light levels) and LIRD groups promote increased retinal astrocytic population, GFAP expression, branching and endpoints, dendritic complexity, and promotes BDNF-astrocyte interaction. In contrast, LIRD animals that were inactive had significant reductions in all measured parameters. Our findings indicate that exercise is sufficient to rescue retinal astrocyte morphology in a LIRD model maintaining branching and dendritic arborization similar to retinal astrocytes that are not undergoing degeneration. These studies provide essential information to current knowledge gaps in regards to exercise-induced neuroprotection and will additionally provide knowledge in exercise intervention optimization as a rehabilitative method.

Significance statement

This study represents an essential step in determining the cell-types governing and morphological alterations elicited from exercise which may provide neural repair and protection. Similar to astrocytes in the brain, retinal astrocytes alter their morphology in response to exercise. Our studies demonstrate exercise promotes increased interactions between retinal astrocytes and neural growth factors in healthy retinas as well as in retinas undergoing degeneration, which may ultimately protect dying retinal neurons. These studies provide insight into the potential neuroprotective role astrocytes play in neurodegenerative diseases.
Altered neutrophil phenotype and function in non-ICU hospitalised COVID-19 patients correlated with disease severity
Authors: Belchamber KBR , Thein OS , Hazeldine J , Grudzinska FS , Hughes MJ , Jasper AE , Yip KP , Sapey E , Parekh D , Thickett DR , Scott A
Published: June 2021

Rational

Infection with the SARS-CoV2 virus is associated with elevated neutrophil counts. Evidence of neutrophil dysfunction in COVID-19 is based predominantly on transcriptomics or single functional assays. Cell functions are interwoven pathways, and so understanding the effect of COVID-19 across the spectrum of neutrophil function may identify tractable therapeutic targets.

Objectives

Examine neutrophil phenotype and functional capacity in COVID-19 patients versus age-matched controls (AMC)

Methods

Isolated neutrophils from 41 hospitalised, non-ICU COVID-19 patients and 23 AMC underwentex vivoanalyses for migration, bacterial phagocytosis, ROS generation, NET formation (NETosis) and cell surface receptor expression. DNAse 1 activity was measured, alongside circulating levels of cfDNA, MPO, VEGF, IL-6 and sTNFRI. All measurements were correlated to clinical outcome. Serial sampling on day 3-5 post hospitalisation were also measured.

Results

Compared to AMC, COVID-19 neutrophils demonstrated elevated transmigration (p=0.0397) and NETosis (p=0.0366), but impaired phagocytosis (p=0.0236) associated with impaired ROS generation (p<0.0001). Surface expression of CD54 (p<0.0001) and CD11c (p=0.0008) was significantly increased and CD11b significantly decreased (p=0.0229) on COVID-19 patient neutrophils. COVID-19 patients showed increased systemic markers of NETosis including increased cfDNA (p=0.0153) and impaired DNAse activity (p<0.0.001). MPO (p<0.0001), VEGF (p<0.0001), TNFRI (p<0.0001) and IL-6 (p=0.009) were elevated in COVID-19, which positively correlated with disease severity by 4C score.

Conclusion

COVID-19 is associated with neutrophil dysfunction across all main effector functions, with altered phenotype, elevated migration, impaired antimicrobial responses and elevated NETosis. These changes represent a clear mechanism for tissue damage and highlight that targeting neutrophil function may help modulate COVID-19 severity.
The NF-κB pathway controls H3K9me3 levels at intronic LINE-1 elements and hematopoietic stem cell gene expression in cis
Authors: Pelinski Yanis , Hidaoui Donia , Stolz Anne , Hermetet François , Chelbi Rabie , Diop M’boyba Khadija , Chioukh Amir M. , Porteu Françoise , Elvira-Matelot Emilie
Published: June 2021

Ionizing radiations (IR) alter hematopoietic stem cell (HSC) function on the long-term, but the mechanisms underlying these effects are still poorly understood. We recently showed that IR induces the derepression of L1Md, the mouse young subfamilies of LINE-1/L1 retroelements. L1 contribute to gene regulatory networks. However, how L1Md are derepressed and impact HSC gene expression are not known. Here we show that IR triggers genome-wide H3K9me3 decrease that occurs mainly at L1Md. Loss of H3K9me3 at intronic L1Md harboring NF-κB binding sites motifs but not at promoters is associated with the repression of HSC specific genes. This is correlated with reduced NFKB1 repressor expression. TNF-α-treatment before IR rescued all these effects and prevented IR-induced HSC loss of function in vivo. This TNF-α/NF-κB/H3K9me3/L1Md axis might be important to maintain of HSCs while allowing expression of immune genes during myeloid regeneration or damage-induced bone marrow ablation.
The LysR-type transcriptional regulator BsrA (PA2121) controls vital metabolic pathways in Pseudomonas aeruginosa
Authors: Modrzejewska Magdalena , Kawalek Adam , Bartosik Aneta Agnieszka
Published: June 2021

Pseudomonas aeruginosa, a facultative human pathogen causing nosocomial infections, has complex regulatory systems involving many transcriptional regulators. LTTR (LysR-Type Transcriptional Regulator) family proteins are involved in the regulation of various processes including stress responses, motility, virulence and amino acid metabolism. The aim of this study was to characterize the LysR-type protein BsrA (PA2121), previously described as a negative regulator of biofilm formation in P. aeruginosa. Genome wide identification of BsrA binding sites using ChIP-seq revealed 765 BsrA-bound regions in the P. aeruginosa PAO1161 genome, including 367 sites in intergenic regions. The motif T-N11-A was identified within sequences bound by BsrA. Transcriptomic analysis showed altered expression of 157 genes in response to BsrA excess, of which 35 had a BsrA binding site within their promoter regions, suggesting a direct influence of BsrA on the transcription of these genes. BsrA-repressed loci included genes encoding proteins engaged in key metabolic pathways such as the tricarboxylic acid cycle. The panel of loci possibly directly activated by BsrA, included genes involved in pili/fimbriae assembly as well as secretion and transport systems. In addition, DNA pull-down and regulatory analyses showed the involvement of PA2551, PA3398 and PA5189 in regulation of bsrA expression, indicating that this gene is part of an intricate regulatory network. Taken together, these findings reveal the existence of a BsrA regulon, which performs important functions in P. aeruginosa.

IMPORTANCE

This study shows that BsrA, a LysR-type transcriptional regulator from P. aeruginosa, previously identified as a repressor of biofilm synthesis, is part of an intricate global regulatory network. BsrA acts directly and/or indirectly as the repressor and/or activator of genes from vital metabolic pathways (e.g. pyruvate, acetate, tricarboxylic acid cycle), and is involved in control of transport functions and the formation of surface appendages. Expression of the bsrA gene is increased in the presence of antibiotics, which suggests its induction in response to stress, possibly reflecting the need to redirect metabolism under stressful conditions. This is particularly relevant for the treatment of infections caused by P. aeruginosa. In summary, the findings of this study demonstrate that the BsrA regulator performs important roles in carbon metabolism, biofilm formation and antibiotic resistance in P. aeruginosa.
The effect of hull fineness ratio and fin parameters on the optimization of tethered aerostat
Authors: Mahmood Khurrum , Ismail Norilmi Amilia
Published: June 2021

Purpose

This paper aims to optimize the mass of a tethered aerostat to achieve optimum hull volume, and fins to generate aerodynamic lift to reduce the blow-by.

Design/methodology/approach

The design code of aerostat involving structure, aerostatics, aerodynamics and stability has been developed using MATLAB®. The design code is used to obtain the baseline configuration for a tactical aerostat mission by using the statistical values of the hull fineness ratio and the fin parameters of in-service aerostats. The effect of the design variables that include the hull fineness ratio, fin area and fin position on the aerostat mass and blow-by is determined through sensitivity analysis. The aerostat is optimized with an objective function of minimization of mass for the bounded values of design variables and taking blow-by limit as a constraint.

Findings

This study reveals that the simultaneous optimization of the aerostat hull fineness ratio, fin area and fin position results in an improvement in the design. The aerostat design with optimum values of these parameters helps in a reduction in its size and mass without compromising the blow-by limits.

Research limitations/implications

This study has been conducted by keeping the hull shape constant by selecting standard National Physics Laboratory envelope shape. The aerodynamic model used in the design code is based on empirical relationships that can be improved in future studies that can use high fidelity aerodynamic models using CFD based surrogate models.

Originality/value

The previous studies on optimization of aerostats are limited to hull envelope shape only, whereas this paper presents the optimization of the hull and fin together. The optimized configuration obtained has a reduced mass and can operate within the specified blow-by limits.
Co-operation and consistency: a global survey of professionals involved in reopening schools during the COVID-19 pandemic
Authors: Gray Nicola J. , Jourdan Didier
Published: June 2021

Purpose

During the 2020 COVID-19 pandemic, schools closed in haste and were expected to create virtual learning opportunities for their students while they waited to see when and how they might re-open. National governments issued reopening guidance at varying speeds. The purpose of this study was to invite health and education professionals to share what was happening in their country about school reopening in terms of the features and implications of the guidance issued.

Design/methodology/approach

A qualitative study. Initial interviews informed a semi-structured questionnaire distributed through the global community of UNESCO Chair ‘Global Health and Education’ and partner organisations. Its aim was to collect, analyse and share globally relevant knowledge and practices about school reopening.

Findings

There were 192 useable responses from 43 countries and territories and 1 multi-country region. 20 of these, mainly in the Global North, had received reopening guidance, 23 were still waiting and 1 had not closed its schools. Guidance prioritised public health measures like social distancing, with less emphasis on education impacts. Success came from partnerships between schools, families and local authorities, consistent guidance and enough time and resources for implementation. Fear of infection led to significant absenteeism among students and staff. Respondents waiting for guidance, mainly in the Global South, shared similar concerns and expectations.

Originality/value

Describing first-hand practices and perspectives of health and education professionals from diverse countries and territories about reopening schools.
Barriers and drivers of environmental sustainability: Australian hotels
Authors: Khatter Ajay , White Leanne , Pyke Joanne , McGrath Michael
Published: June 2021

Purpose

The paper presents the findings of research into the barriers to and drivers of environmentally sustainable policies and practices (ESPPs) in the Australian hotel industry. This study aims to explore these drivers and barriers from the perspective of hotel managers and involve a range of hotels with different hotel industry profiles and management structures.

Design/methodology/approach

The study conducted one-on-one interviews with hotel managers to explore the barriers to and drivers of ESPPs. The purpose of the sample and sample size was to ensure representation of different segments of the hotel industry to include international chain affiliated hotels, Australian chain affiliated hotels and independent hotels.

Findings

An analysis of the findings suggests that the major barriers to implementing and sustaining environmental sustainability in the Australian hotel industry are time, financial challenges, availability of resources and the views and imperatives of hotel owners and shareholders. The major drivers are financial, marketing, owner and shareholder interests and guest preferences. These stakeholders play a major role in creating both barriers and drivers.

Research limitations/implications

Based on the results, this study can modify the application of stakeholder theory to a degree and argue that stakeholders need to co-operate further to drive sustainability. This study demonstrates that management of environmental sustainability is a challenge for many hotels and there is a particular need for small and independent hotels to embrace environmental sustainability to keep pace with their larger counterparts.

Originality/value

This study is broadly informed by the stakeholder theory. Owners, shareholders and associated stakeholders have a significant influence over environmental sustainability in the Australian hotel industry and they create both drivers and barriers. Responses from hotel managers in this research demonstrate that owners act as a barrier to as well as a driver of environmental sustainability initiatives in the Australian hotel industry.
Civil society organisations’ management dynamics and social value creation in the post-conflict volatile contexts pre and during COVID-19
Authors: Arslan Ahmad , Kamara Samppa , Golgeci Ismail , Tarba Shlomo Yedidia
Published: June 2021

Purpose

The current paper aims to address the management dynamics of civil society organisations (CSOs) in volatile contexts. Along with analysing CSOs’ management dynamics at a general level, it also offers specific insights into their management strategies in response to COVID-19 pandemic.

Design/methodology/approach

This study uses a qualitative research design, where in-depth case studies are undertaken with four CSOs operating in post-conflict volatile Sub-Saharan African economies of Liberia and Sierra Leone.

Findings

Findings revealed that multiple stakeholder management plays an important role in social value creation by CSOs. The findings further state that, in volatile contexts, CSOs appear to have more legitimacy than state functionaries due to their capabilities in dealing with political pressures and conflict sensitivities. The findings also revealed that case CSOs operating in Liberia and Sierra Leone were quick to respond to the COVID-19 pandemic by adjusting their working routines accordingly by switching to online working where possible and repurposing their management strategies. This repurposing of management strategies focussed on minimising economic disruptions caused by COVID-19 and continuing to create social value by helping youth and farmers particularly.

Originality/value

This paper contributes to the extant literature by being one of the first studies, highlighting the specificities of CSO management in volatile (especially Sub-Saharan African post-conflict) contexts and contributes to the literature streams on multiple stakeholder management and social value creation. To the best of the authors’ knowledge, the current paper is also one the first study to address the management strategies of case CSOs in response to the ongoing Covid-19 pandemic in Liberia and Sierra Leone.
Toward a carbon neutral campus: a scalable approach to estimate carbon storage and biosequestration, an example from University of Michigan
Authors: Tonietto Rebecca , O’Brien Lara , Van Haitsma Cyrus , Su Chenyang , Blankertz Nicole , Mosiniak Hannah Grace Shaheen , Short Caleb , Dawson Heather Ann
Published: June 2021

Purpose

The University of Michigan (U-M) is planning its course toward carbon neutrality. A key component in U-M carbon accounting is the calculation of carbon sinks via estimation of carbon storage and biosequestration on U-M landholdings. Here, this paper aims to compare multiple remote sensing methods across U-M natural lands and urban campuses to determine the accurate and efficient protocol for land assessment and ecosystem service valuation that other institutions may scale as relevant.

Design/methodology/approach

This paper tested three remote sensing methods to determine land use and land cover (LULC), namely, unsupervised classification, supervised classification and supervised classification incorporating delineated wetlands. Using confusion matrices, this paper tested remote sensing approaches to ground-truthed data, the paper obtained via field-based vegetation surveys across a subset of U-M landholdings.

Findings

In natural areas, supervised classification incorporating delineated wetlands was the most accurate and efficient approach. In urban settings, maps incorporating institutional knowledge and campus tree surveys better estimated LULC. Using LULC and literature-based carbon data, this paper estimated that U-M lands store 1.37–3.68 million metric tons of carbon and sequester 45,000–86,000 Mt CO2e/yr, valued at $2.2m–$4.3m annually ($50/metric ton, social cost of carbon).

Originality/value

This paper compared methods to identify an efficient and accurate remote sensing methodology to identify LULC and estimate carbon storage, biosequestration rates and economic values of ecosystem services provided.
Follow-the-leader motion strategy for multi-section continuum robots based on differential evolution algorithm
Authors: Gao GuoHua , Wang Pengyu , Wang Hao
Published: June 2021

Purpose

The purpose of this paper is to present a follow-the-leader motion strategy for multi-section continuum robots, which aims to make the robot have the motion ability in a confined environment and avoid a collision.

Design/methodology/approach

First, the mechanical design of a multi-section continuum robot is introduced and the forward kinematic model is built. After that, the follow-the-leader motion strategy is proposed and the differential evolution (DE) algorithm for calculating optimal posture parameters is presented. Then simulations and experiments are carried out on a series of predefined paths to analyze the performance of the follow-the-leader motion.

Findings

The follow-the-leader motion can be well performed on the continuum robots this study proposes in this research. The experimental results show that the deviation from the path is less than 9.7% and the tip error is no more than 15.6%.

Research limitations/implications

Currently, the follow-the-leader motion is affected by the following factors such as gravity and continuum robot design. Furthermore, the position error is not compensated under open-loop control. In future work, this paper will improve the accuracy of the robot and introduce a closed-loop control strategy to improve the motion accuracy.

Originality/value

The main contribution of this paper is to present an algorithm to generate follow-the-leader motion of the continuum robot based on DE. This method is suitable for solving new arrangements in the process of following a nonlinear path. Then, it is expected to promote the engineering application of the continuum robot.
Target tracking based on standard hedging and feature fusion for robot
Authors: Chan Sixian , Tao Jian , Zhou Xiaolong , Wu Binghui , Wang Hongqiang , Chen Shengyong
Published: June 2021

Purpose

Visual tracking technology enables industrial robots interacting with human beings intelligently. However, due to the complexity of the tracking problem, the accuracy of visual target tracking still has great space for improvement. This paper aims to propose an accurate visual target tracking method based on standard hedging and feature fusion.

Design/methodology/approach

For this study, the authors first learn the discriminative information between targets and similar objects in the histogram of oriented gradients by feature optimization method, and then use standard hedging algorithms to dynamically balance the weights between different feature optimization components. Moreover, they penalize the filter coefficients by incorporating spatial regularization coefficient and extend the Kernelized Correlation Filter for robust tracking. Finally, a model update mechanism to improve the effectiveness of the tracking is proposed.

Findings

Extensive experimental results demonstrate the superior performance of the proposed method comparing to the state-of-the-art tracking methods.

Originality/value

Improvements to existing visual target tracking algorithms are achieved through feature fusion and standard hedging algorithms to further improve the tracking accuracy of robots on targets in reality.