bluuebunny/crossref_metadata_2025 huggingface dataset:
The Associations Between Bitter and Fat Taste Sensitivity, and Dietary Fat Intake: Are They Impacted by Genetic Predisposition?
Authors: Graham Catherine Anna-Marie , Pilic Leta , Mcgrigor Ella , Brown Megan , Easton Isabelle Jane , Kean Jonathan Nyuma , Sarel Verity , Wehliye Yasmin , Davis Natalie , Hares Nisrin , Barac Deanna , King Alexandra , Mavrommatis Yiannis
Published: June 2021

A relationship between bitter and fat taste sensitivity, CD36 rs1761667 and TAS2R38 has been demonstrated. However, research is scarce and does not take diet into account. This study aimed to explore associations between genetics, fat and bitter taste sensitivity and dietary fat intake in healthy UK adults. A cross-sectional study was carried out on 88 Caucasian participants (49 females and 39 males aged 35 ± 1 years; body mass index 24.9 ± 0.5 kg/m2). Bitter taste sensitivity was assessed using phenylthiocarbamide (PTC) impregnated strips and the general Labeled Magnitude Scale. Fat taste sensitivity was assessed by the Ascending Forced Choice Triangle Procedure and dietary intake with a semi-quantitative food frequency questionnaire. Genotyping for rs713598, rs1726866, rs10246939, and rs1761667 was performed. Participants with TAS2R38 PAV/PAV diplotype perceived PTC strips as more bitter than groups carrying AVI haplotypes (AVI/AVI, P = 1 × 10−6; AVI/AAV, P = 0.029). CD36 rs1761667 was associated with fat taste sensitivity (P = 0.008). A negative correlation between bitter taste sensitivity and saturated fat intake was observed (rs = −0.256, P = 0.016). When combining the CD36 genotypes and TAS2R38 diplotypes into one variable, participants carrying both TAS2R38 AVI haplotype and CD36 A allele had a higher intake of saturated fat compared to carriers of CD36 GG genotype or TAS2R38 PAV/PAV and PAV/AAV diplotypes (13.8 ± 0.3 vs. 12.6 ± 0.5%TEI, P = 0.047) warranting further exploration in a larger cohort.
Cost-Effectiveness and Impact of a Targeted Age- and Incidence-based West Nile Virus Vaccine Strategy
Authors: Curren Emily J , Shankar Manjunath B , Fischer Marc , Meltzer Martin I , Erin Staples J , Gould Carolyn V
Published: June 2021

Background

West Nile virus (WNV) is the leading cause of arboviral disease in the United States and is associated with significant morbidity and mortality. A previous analysis found that a vaccination program targeting persons aged ≥60 years was more cost-effective than universal vaccination, but costs remained high.

Methods

We used a mathematical Markov model to evaluate cost-effectiveness of an age- and incidence-based WNV vaccination program. We grouped states and large counties (≥100 000 persons aged ≥60 years) by median annual WNV incidence rates from 2004 to 2017 for persons aged ≥60 years. We defined WNV incidence thresholds, in increments of 0.5 cases per 100 000 persons ≥60 years. We calculated potential cost per WNV vaccine-prevented case and per quality adjusted life-years (QALYs) saved.

Results

Vaccinating persons aged ≥60 years in states with an annual incidence of WNV neuroinvasive disease of ≥0.5 per 100 000 resulted in approximately half the cost per health outcome averted compared to vaccinating persons aged ≥60 years in the contiguous United States. This approach could potentially prevent 37% of all neuroinvasive disease cases and 63% of WNV-related deaths nationally. Employing such a threshold at a county level further improved cost-effectiveness ratios while preventing 19% and 30% of WNV-related neuroinvasive disease cases and deaths, respectively.

Conclusions

An age- and incidence-based WNV vaccination program could be a more cost-effective strategy than an age-based program while still having a substantial impact on lowering WNV-related morbidity and mortality.
A case of buprenorphine-precipitated withdrawal managed with high-dose buprenorphine
Authors: Quattlebaum Thomas H N , Kiyokawa Miki , Murata Kayla A
Published: June 2021

Background

Buprenorphine–naloxone has a very high affinity for the mu-receptor and can cause precipitated opioid withdrawal, typically more severe than withdrawal that occurs naturally, when administered while a full mu-opioid receptor agonist remains in a person’s system. To avoid precipitated withdrawal, one needs to be in mild to moderate opioid withdrawal at the time of buprenorphine-naloxone induction. Recently, there have been reported cases of precipitated withdrawal occurring in patients taking fentanyl knowingly or unknowingly, despite them being in adequate opioid withdrawal at the time of induction. When this occurs, the current recommendation is to provide 2 mg of buprenorphine–naloxone every 1–2 hours.

Objectives

Describe a case of successful management of buprenorphine-precipitated withdrawal with escalation of the dose of buprenorphine and highlight implications for future management.

Methods

We present a case of a patient with a history of opioid use disorder who was in moderate opioid withdrawal at the time of buprenorphine–naloxone induction and experienced precipitated withdrawal after buprenorphine–naloxone administration.

Results

High-dose buprenorphine–naloxone was given to the patient and precipitated withdrawal subsided after receiving a total of 20 mg. On the next day, the patient had no symptoms of opioid withdrawal and is currently maintained on 16 mg/day.

Conclusion

With the rising prevalence of fentanyl-laced drugs, increased instances of precipitated withdrawal are likely to be encountered. In cases of precipitated withdrawal, giving a high dose of buprenorphine–naloxone rapidly is safe and will allow rapid reversal of withdrawal symptoms.
The Lived Experience of Already-Lonely Older Adults During COVID-19
Authors: Bundy Henry , Lee Heather M , Sturkey Kim N , Caprio Anthony J
Published: June 2021

Background and Objectives

From the outset of the coronavirus disease 2019 (COVID-19) pandemic, analysts warned that older populations, due to their age, chronic illnesses, and lack of technological facility, would suffer disproportionately from loneliness as they sheltered in place indefinitely. Several studies have recently been published on the impact of COVID-19-related loneliness among older populations, but little has been written about the experiences of already-lonely older individuals; those who had lived with persistent loneliness before the advent of COVID-19. This qualitative study sought to understand how already-lonely older individuals navigated and endured the social isolation of the pandemic.

Research Design and Methods

Twelve semistructured interviews were conducted with individuals aged 65 or older who scored a 6 or above on the 3-item UCLA Loneliness Risk screening tool. Interviews were coded using the constant comparative method. Themes and understandings of loneliness that reoccurred within and across interviews were identified and collected.

Results

Already-isolated older interviewees did not necessarily experience the abject loneliness hypothesized by analysts. Most interviewees used longstanding arrangements, in place to mitigate loneliness and endure social isolation, to manage the social deprivation of COVID-19. As a result, their loneliness did not compound during long bouts of mandated social isolation. To the contrary, loneliness during the pandemic appeared to carry a new valence for interviewees, as COVID-19 imbued their isolation with new meaning, rendering their loneliness necessary and responsible.

Discussion and Implications

Exploring individuals’ subjective perceptions of loneliness can help provide a deeper understanding of what it means to be isolated and alone during COVID-19 and aid in designing strategies to mitigate loneliness.
Spatial, temporal and cell-type-specific expression profiles of genes encoding heparan sulfate biosynthesis enzymes and proteoglycan core proteins
Authors: Moon Sohyun , Zhao Ying-Tao
Published: June 2021

Heparan sulfate (HS) is a linear polysaccharide found in almost all animal cells and plays an important role in various biological processes. HS functions mainly via covalently binding to core proteins to form HS proteoglycans (HSPGs), which are heterogeneous in the lengths of the HS chain, the modifications on HS and the core proteins. The molecular mechanisms underlying HSPG heterogeneity, although widely studied, are not yet fully defined. The expression profiles of HS biosynthesis enzymes and HSPG core proteins likely contribute to the HSPG heterogeneity, but these expression profiles remain poorly characterized. To investigate the expression profiles of genes encoding HS biosynthesis enzymes and HSPG core proteins, we systematically integrated the publicly available RNA sequencing data in mice. To reveal the spatial expression of these genes, we analyzed their expression in 21 mouse tissues. To reveal the temporal expression of these genes, we analyzed their expression at 17 time points during the mouse forebrain development. To determine the cell-type-specific expression of these genes, we obtained their expression profiles in 23 cell types in the mouse cerebral cortex by integrating single nucleus RNA sequencing data. Our findings demonstrate the spatial, temporal and cell-type-specific expression of genes encoding HS biosynthesis enzymes and HSPG core proteins and represent a valuable resource to the HS research community.
The 2019 Morocco Model BIT: Moving Forwards, Backwards or Roundabout in Circles?
Authors: Banerjee Arpan , Weber Simon
Published: June 2021

The Moroccan Model Bilateral Investment Treaty (BIT) (2019) adds to a growing body of ‘new-generation’ model BITs that have fuelled the conversation on reforming the investment arbitration system. Broadly speaking, such agreements have attempted to rethink means of dispute resolution and traditional investment protection standards while adding detailed investor obligations and standards of conduct. In that context, this article discusses the provisions of the Moroccan Model BIT (2019), highlighting not only progressive developments but also areas of concern. Upon comparing the provisions of the BIT with those of other ‘new-generation’ investment agreements, as well as existing treaty practice, the authors offer the following findings.
Reflection on modern methods: statistical, policy and ethical implications of using age-standardized health indicators to quantify inequities
Authors: Thurber Katherine A , Thandrayen Joanne , Maddox Raglan , Barrett Eden M , Walker Jennie , Priest Naomi , Korda Rosemary J , Banks Emily , Williams David R , Lovett Raymond
Published: June 2021

Methods for calculating health indicators profoundly influence understanding of and action on population health and inequities. Age-standardization can be useful and is commonly applied to account for differences in age structures when comparing health indicators across groups. Age-standardized rates have well-acknowledged limitations, including that they are relative indices for comparison, and not accurate measures of actual rates where the age structures of groups diverge. This paper explores these limitations, and demonstrates alternative approaches through a case study quantifying mortality rates within the Aboriginal and Torres Strait Islander (Indigenous) population of Australia and inequities compared with the non-Indigenous population, over 2001–16. Applying the Australian Standard Population, the Aboriginal and Torres Strait Islander age-standardized mortality rate was more than double the crude mortality rate in 2001 and 2016, inflated through high weighting of older age groups. Despite divergent population age structures, age-standardized mortality rates remain a key policy metric for measuring progress in reducing Indigenous-non-Indigenous inequities in Australia. Focusing on outcomes age-standardized to the total population can obscure inequities, and denies Aboriginal and Torres Strait Islander peoples and communities valid, actionable information about their health and well-being. Age-specific statistics convey the true magnitude of health risks and highlight high-risk subgroups. When requiring standardization, standardizing to a population-specific standard (here, an Indigenous standard) generates metrics centred around and reflective of reality for the population of focus, supporting communities’ self-determination to identify priorities and informing resource allocation and service delivery. The principles outlined here apply across populations, including Indigenous and other populations internationally.
Type 1 Innate Lymphoid Cell and Natural Killer Cells Are Sources of Interferon-γ and Other Inflammatory Cytokines Associated With Distinct Clinical Presentation in Early Dengue Infection
Authors: Quintino-de-Carvalho Iracema Luisa , Gonçalves-Pereira Marcela Helena , Faria Ramos Michele , de Aguiar Milhim Bruno Henrique Gonçalves , Da Costa Último Libânio , Santos Érika Gonçalves , Nogueira Maurício Lacerda , Da Costa Santiago Helton
Published: June 2021

Background

Increased levels of inflammatory cytokines are associated with severe dengue evolution, but the source of such hypercytokinemia is elusive. We investigated the contribution of innate lymphocytes, innate lymphoid cells (ILCs), and natural killer (NK) cells in cytokine production in early dengue infection.

Methods

Peripheral blood mononuclear cells of individuals with dengue without warning signs (DWS–) and dengue with warning signs and severe dengue (SD) presentation combined (DWS+) were obtained between 2 and 7 days since fever onset and submitted to flow cytometry without specific antigen stimulation to evaluate cytokines in ILC and NK cell subpopulations.

Results

ILCs and NK cells were found to be important sources of cytokines during dengue. ILCs of the DWS+/SD group displayed higher production of interferon gamma (IFN-γ) and interleukin (IL) 4/IL-13 when compared to DWS– individuals. On the other hand, NK Eomes+ cells of DWS– patients displayed higher IFN-γ production levels compared with the DWS+/SD group. Interestingly, when NK cells were identified by CD56 expression, DWS+/SD displayed higher frequency of IL-17 production compared with the DWS– group.

Conclusions

These results indicate that ILCs and NK cells are important sources of inflammatory cytokines during acute dengue infection and display distinct profiles associated with different clinical forms.
Dietary dimethylglycine sodium salt supplementation improves growth performance, redox status, and skeletal muscle function of intrauterine growth-restricted weaned piglets
Authors: Bai Kaiwen , Jiang Luyi , Li Qiming , Zhang Jingfei , Zhang Lili , Wang Tian
Published: June 2021

Few studies have focused on the role of dimethylglycine sodium (DMG-Na) salt in protecting the redox status of skeletal muscle, although it is reported to be beneficial in animal husbandry. This study investigated the beneficial effects of DMG-Na salt on the growth performance, longissimus dorsi muscle (LM) redox status, and mitochondrial function in weaning piglets that were intrauterine growth restricted (IUGR). Ten normal birth weight (NBW) newborn piglets (1.53 ± 0.04 kg) and 20 IUGR newborn piglets (0.76 ± 0.06 kg) from 10 sows were obtained. All piglets were weaned at 21 d of age and allocated to the three groups with 10 replicates per group: NBW weaned piglets fed a common basal diet (N); IUGR weaned piglets fed a common basal diet (I); IUGR weaned piglets fed a common basal diet supplemented with 0.1% DMG-Na (ID). They were slaughtered at 49 d of age to collect the serum and LM samples. Compared with the N group, the growth performance, LM structure, serum, and, within the LM, mitochondrial redox status, mitochondrial respiratory chain complex activity, energy metabolites, redox status-related, cell adhesion-related, and mitochondrial function-related gene expression, and protein expression deteriorated in group I (P < 0.05). The ID group showed improved growth performance, LM structure, serum, and, within the LM, mitochondrial redox status, mitochondrial respiratory chain complex activity, energy metabolites, redox status-related, cell adhesion-related, and mitochondrial function-related gene expression, and protein expression compared with those in the I group (P < 0.05). The above results indicated that the DMG-Na salt treatment could improve the LM redox status and mitochondrial function in IUGR weaned piglets via the nuclear factor erythroid 2-related factor 2/sirtuin 1/peroxisome proliferator-activated receptorγcoactivator-1α network, thus improving their growth performance.
Water Balance and Desiccation Tolerance of the Invasive South American Tomato Pinworm
Authors: Tarusikirwa Vimbai L , Cuthbert Ross N , Mutamiswa Reyard , Gotcha Nonofo , Nyamukondiwa Casper
Published: June 2021

Temperature and dehydration stress are two major co-occurring environmental stressors threatening the physiology, biochemistry, and ecology of insects. As such, understanding adaptive responses to desiccation stress is critical for predicting climate change impacts, particularly its influence on insect invasions. Here, we assessed water balance and desiccation resistance of the invasive Tuta absoluta (Meyrick, 1917) (Lepidoptera: Gelechiidae), and infer how eco-physiology shapes its niche. We measured basal body water and lipid content, water loss rates (WLRs), and desiccation resistance in larvae (second to fourth instars) and adults. Body -water, -lipid, and WLRs significantly varied across life stages. Second instars recorded the lowest while fourth instars exhibited the highest body water and lipid content. Adult body water and lipid content were higher than second and third instars and lower than fourth instars while proportion of body water and lipid contents were highest in adults and second larval instars respectively. Water loss rates were significantly highest in fourth-instar larvae compared to other life stages, but differences among stages were less apparent at longer exposure durations (48 h). Desiccation resistance assays showed that second instars had greatest mortality while fourth-instar larvae and adults were the most desiccation tolerant. Our results show that T. absoluta fourth-instar larvae and adults are the most resilient developmental stages and potentially contribute most to the invasion success of the pest in arid environments. Incorporation of these species-specific eco-physiological traits in predictive models can help refine invasive species potential spread under changing climates.
The Cause of all Humanity
Authors: Eboe-Osuji Chile
Published: June 2021

After years of uneasy interactions between successive administrations of the United States and the International Criminal Court (ICC) — ranging from apathy to indifference to tacit utilitarian engagement behind the scenes — the administration of President Donald Trump unleashed the most intense aggression against the Court, marked by direct coercive measures against the Court’s officials. This followed relentless prior threats of such actions and promises to do more harm. Since other international institutions including the World Health Organization, the World Trade Organization, and the Human Rights Council have also been on the receiving end of rough treatment from Mr Trump, it is evident that the experience of the ICC under his administration was not entirely unique, although the particular circumstances may have been so. The new administration of Mr Biden has signalled an intention to reset US foreign policy — and has started this process — by reversing the more aggressive aspects of Mr Trump’s stance. In relation to the ICC, this change should go beyond merely reversing Mr Trump’s coercive measures. It should include positive support for the Court, given America’s leading role in inspiring its creation and the Court’s raison d’être which remains the cause of all humanity.
Discovery of an alternative pathway of peptidoglycan biosynthesis: A new target for pathway specific inhibitors
Authors: Ogasawara Yasushi , Dairi Tohru
Published: June 2021

Peptidoglycan in bacterial cell walls is a biopolymer consisting of sugars and amino acids and plays important role in maintaining cell integrity from the environment. Its biosynthesis is a major target for antibiotics and the genes and enzymes involved in the biosynthetic pathway have been well studied. However, we recently identified an alternative pathway in the early stage of peptidoglycan biosynthesis in Xanthomonas oryzae, a plant pathogen causing bacterial blight disease of rice. The distribution of the alternative pathway is limited to relatively few bacterial genera that contain many pathogenic species, including Xylella and Stenotrophomonas, besides Xanthomonas. Thus, the alternative pathway is an attractive target for the development of narrow-spectrum antibiotics specific to pathogens. In this minireview, we summarize the discovery of the alternative pathway and identification of its specific inhibitors.
Color Preference for Host-Seeking Activity ofAedes albopictusandCulex pipiens(Diptera: Culicidae)
Authors: Jung Sun Ho , Kim Dongmin , Jung Ki-Suck , Lee Dong-Kyu
Published: June 2021

A cue for long-range vision allows mosquitoes to identify hosts and differentiate the ecological niches (e.g., habitats). However, the visual factors involved in attracting mosquitoes to a host are complex and have not been fully understood. Therefore, we assessed color preference to Aedes albopictus (Skuse) and Culex pipiens (Conquillett) as diurnal and nocturnal species, respectively, using seven fundamental colors including black, white, red, yellow, green, blue, and purple with each trap at 100 lux in a laboratory. We used a binary behavioral assay using the Mosquito Preference Index (MPI) as a preference ratio with a range of 0–1. Our analyses showed that Ae. albopictus had a greater response to black (MPIs, 0.7), followed closely by red, blue, and purple (MPIs, 0.6). We also found that red, blue, and purple were significantly higher (P < 0.05) than those of green (MPI, 0.5), white (MPI, 0.3), and yellow (MPI, 0.2). Similarly, the MPIs for Cx. pipiens were significantly higher at black and red (MPIs, 0.7; P < 0.05) compare to those of white and yellow (MPIs, 0.3; P < 0.05). The color preference of Ae. albopictus showed significant correlation to luminous intensities (L-value) (r = −0.640; P = 0.000) and blue intensities (b-value) (r = −0.372; P = 0.000) for all seven colors. In addition, Cx. pipiens negatively correlated (r = −0.703; P = 0.000) between color preference and L-value. Our analyses provide a greater understanding of how color plays a role in visual sensory stimuli, and how that could potentially affect mosquito host-seeking behavior.
Alamandine protects against renal ischaemia–reperfusion injury in rats via inhibiting oxidative stress
Authors: Zhu Jue , Qiu Jian-Guo , Xu Wei-Tao , Ma Hong-Xiang , Jiang Ke
Published: June 2021

Objective

This study was to determine whether alamandine (Ala) could reduce ischaemia and reperfusion (I/R) injury of kidney in rats.

Methods

Renal I/R was induced by an occlusion of bilateral renal arteries for 70 min and a 24-h reperfusion in vivo, and rat kidney proximal tubular epithelial cells NRK52E were exposed to 24 h of hypoxia and followed by 3-h reoxygenation (H/R) in vitro.

Results

The elevated serum creatinine (Cr), blood cystatin C (CysC) and blood urea nitrogen (BUN) levels in I/R rats were inhibited by Ala treatment. Tumour necrosis factor alpha (TNF)-α, IL-1β, IL-6, cleaved caspase-3, cleaved caspase-8 and Bax were increased, and Bcl2 was reduced in the kidney of I/R rats, which were reversed by Ala administration. Ala reversed the increase of TNF-α, IL-1β, IL-6, cleaved caspase-3, cleaved caspase-8 and Bax and the decrease of Bcl2 in the H/R NRK52E cells. Ala could also inhibit the increase of oxidative stress levels in the kidney of I/R rats. NADPH oxidase 1 (Nox1) overexpression reversed the improving effects of Ala on renal function, inflammation and apoptosis of I/R rats.

Conclusion

These results indicated that Ala could improve renal function, attenuate inflammation and apoptosis in the kidney of I/R rats via inhibiting oxidative stress.
MHY1485 enhances X-irradiation-induced apoptosis and senescence in tumor cells
Authors: Sun Lue , Morikawa Kumi , Sogo Yu , Sugiura Yuki
Published: June 2021

The mammalian target of rapamycin (mTOR) is a sensor of nutrient status and plays an important role in cell growth and metabolism. Although inhibition of mTOR signaling promotes tumor cell death and several mTOR inhibitors have been used clinically, recent reports have shown that co-treatment with MHY1485, an mTOR activator, enhances the anti-cancer effects of anti-PD-1 antibody and 5-fluorouracil. However, it remains unclear whether MHY1485 treatment alters the effects of radiation on tumor cells. In this study, the radiosensitizing effects of MHY1485 were investigated using murine CT26 and LLC cell lines. We examined mTOR signaling, tumor cell growth, colony formation, apoptosis, senescence, oxidative stress, p21 accumulation and endoplasmic reticulum (ER) stress levels in cells treated with MHY1485 and radiation, either alone or together. We found that MHY1485 treatment inhibited growth and colony formation in both cell lines under irradiation and no-irradiation conditions, results that were not fully consistent with MHY1485’s known role in activating mTOR signaling. Furthermore, we found that combined treatment with MHY1485 and radiation significantly increased apoptosis and senescence in tumor cells in association with oxidative stress, ER stress and p21 stabilization, compared to radiation treatment alone. Our results suggested that MHY1485 enhances the radiosensitivity of tumor cells by a mechanism that may differ from MHY1485’s role in mTOR activation.
Mechanisms of stress response in the root stem cell niche
Authors: Ubogoeva Elena V , Zemlyanskaya Elena V , Xu Jian , Mironova Victoria
Published: June 2021

As plants are sessile organisms unable to escape from environmental hazards, they need to adapt for survival. The stem cell niche in the root apical meristem is particularly sensitive to DNA damage induced by environmental stresses such as chilling, flooding, wounding, UV, and irradiation. DNA damage has been proven to cause stem cell death, with stele stem cells being the most vulnerable. Stress also induces the division of quiescent center cells. Both reactions disturb the structure and activity of the root stem cell niche temporarily; however, this preserves root meristem integrity and function in the long term. Plants have evolved many mechanisms that ensure stem cell niche maintenance, recovery, and acclimation, allowing them to survive in a changing environment. Here, we provide an overview of the cellular and molecular aspects of stress responses in the root stem cell niche.
Jitter radiation: towards TeV-photons of gamma-ray bursts
Authors: Mao Jirong , Wang Jiancheng
Published: June 2021

The synchrotron mechanism has the radiation limit of about 160 MeV, and it is not possible to explain the very high energy (VHE) photons that are emitted by high-energy objects. Inverse Compton scattering as a traditional process is applied for the explanation of the VHE emission. In this paper, jitter radiation, the relativistic electron radiation in the random and small-scale magnetic field, is proposed to be a possible mechanism to produce VHE photons. The jitter radiation frequency is associated with the perturbation field. The spectral index of the jitter radiation is dominated by the kinetic turbulence. We utilize the jitter radiation to explain the gamma-ray burst (GRB 190114C and GRB 180720B) VHE emissions that were recently detected by the Imaging Atmospheric Cherenkov Telescopes. We suggest that this mechanism can be applied to other kinds of VHE sources.
A 21-cm power spectrum at 48 MHz, using the Owens Valley Long Wavelength Array
Authors: Garsden H , Greenhill L , Bernardi G , Fialkov A , Price D C , Mitchell D , Dowell J , Spinelli M , Schinzel F K
Published: June 2021

The Large-aperture Experiment to detect the Dark Age (LEDA) was designed to measure the 21-cm signal from neutral hydrogen at Cosmic Dawn, z ≈ 15–30. Using observations made with the ≈ 200 m diameter core of the Owens Valley Radio Observatory Long Wavelength Array (OVRO–LWA), we present a 2D cylindrical spatial power spectrum for data at 43.1–53.5 MHz (zmedian ≈ 28) incoherently integrated for 4 h, and an analysis of the array sensitivity. Power from foregrounds is localized to a ‘wedge’ within k⊥, $k_\parallel$ space. After calibration of visibilities using five bright compact sources including Vir A, we measure Δ2(k) ≈ 2 × 1012 mK2 outside the foreground wedge, where an uncontaminated cosmological signal would lie, in principle. The measured Δ2(k) is an upper limit that reflects a combination of thermal instrumental and sky noise, and unmodelled systematics that scatter power from the wedge, as will be discussed. By differencing calibrated visibilities for close pairs of frequency channels, we suppress foreground sky structure and systematics, extract thermal noise, and use a mix of coherent and incoherent integration to simulate a noise-dominated power spectrum for a 3000 h observation and z = 16−37. For suitable calibration quality, the resulting noise level, Δ2(k) ≈ 100 mK2 (k = 0.3 Mpc−1), would be sufficient to detect peaks in the 21-cm spatial power spectrum due to early Ly-α and X-ray sources, as predicted for a range of theoretical model parameters.
A low density wave's spiral pattern speed, from the tracer separations (age gradient) across a spiral arm in the Milky Way
Authors: Vallée Jacques P
Published: June 2021

We observe the density wave's angular pattern speed Ωp to be near 12–17 km s−1 kpc−1, by the separation between a typical optical H ii region (from the spiral arm's dust lane) and using a H ii-evolution time model TH ii to yield its relative speed, and independently by the separation between a typical radio maser (from the spiral arm's dust lane) with a maser model. The assumption of a fixed circular rotational speed of the gas and stars with galactic radius is employed (neglecting spiral perturbation at mid-radii, nuclear bar influence at small radii, and tidal effects at large radii).
Fluctuating Environments Maintain Genetic Diversity through Neutral Fitness Effects and Balancing Selection
Authors: Abdul-Rahman Farah , Tranchina Daniel , Gresham David
Published: June 2021

Genetic variation is the raw material upon which selection acts. The majority of environmental conditions change over time and therefore may result in variable selective effects. How temporally fluctuating environments impact the distribution of fitness effects and in turn population diversity is an unresolved question in evolutionary biology. Here, we employed continuous culturing using chemostats to establish environments that switch periodically between different nutrient limitations and compared the dynamics of selection to static conditions. We used the pooled Saccharomyces cerevisiae haploid gene deletion collection as a synthetic model for populations comprising thousands of unique genotypes. Using barcode sequencing, we find that static environments are uniquely characterized by a small number of high-fitness genotypes that rapidly dominate the population leading to dramatic decreases in genetic diversity. By contrast, fluctuating environments are enriched in genotypes with neutral fitness effects and an absence of extreme fitness genotypes contributing to the maintenance of genetic diversity. We also identified a unique class of genotypes whose frequencies oscillate sinusoidally with a period matching the environmental fluctuation. Oscillatory behavior corresponds to large differences in short-term fitness that are not observed across long timescales pointing to the importance of balancing selection in maintaining genetic diversity in fluctuating environments. Our results are consistent with a high degree of environmental specificity in the distribution of fitness effects and the combined effects of reduced and balancing selection in maintaining genetic diversity in the presence of variable selection.
Blasticidin S inhibits mammalian translation and enhances production of protein encoded by nonsense mRNA
Authors: Powers Kyle T , Stevenson-Jones Flint , Yadav Sathish K N , Amthor Beate , Bufton Joshua C , Borucu Ufuk , Shen Dakang , Becker Jonas P , Lavysh Daria , Hentze Matthias W , Kulozik Andreas E , Neu-Yilik Gabriele , Schaffitzel Christiane
Published: June 2021

Deciphering translation is of paramount importance for the understanding of many diseases, and antibiotics played a pivotal role in this endeavour. Blasticidin S (BlaS) targets translation by binding to the peptidyl transferase center of the large ribosomal subunit. Using biochemical, structural and cellular approaches, we show here that BlaS inhibits both translation elongation and termination in Mammalia. Bound to mammalian terminating ribosomes, BlaS distorts the 3′CCA tail of the P-site tRNA to a larger extent than previously reported for bacterial ribosomes, thus delaying both, peptide bond formation and peptidyl-tRNA hydrolysis. While BlaS does not inhibit stop codon recognition by the eukaryotic release factor 1 (eRF1), it interferes with eRF1’s accommodation into the peptidyl transferase center and subsequent peptide release. In human cells, BlaS inhibits nonsense-mediated mRNA decay and, at subinhibitory concentrations, modulates translation dynamics at premature termination codons leading to enhanced protein production.
Association of serum levels of inflammatory markers and adipokines with joint symptoms and structures in participants with knee osteoarthritis
Authors: Zhu Jimin , Ruan Guangfeng , Cen Han , Meng Tao , Zheng Shuang , Wang Yuanyuan , Li Baikun , Zhu Zhaohua , Han Weiyu , Winzenberg Tania , Wluka Anita E , Cicuttini Flavia , Wang Binghui , Ding Changhai
Published: June 2021

Objective

To investigate the longitudinal associations of serum inflammatory markers and adipokines with joint symptoms and structures in participants with knee OA.

Methods

Two hundred participants (46.5% female, mean age 63.1 years, mean BMI 29.5 kg/m2) from Tasmania, part of the VIDEO (Vitamin D Effect on OA) study, were randomly selected in the current study. Serum levels of 19 biomarkers, scores of WOMAC and MRI-assessed knee structures were evaluated at baseline and month 24. The patterns of biomarkers were derived from principal component analysis and their association with knee symptoms and structures were examined using adjusted generalized estimating equations.

Results

Five components explained 78% of the total variance. IL-1β, -2, -4, -6, -8, -17 A, -17 F, -21, -22 and -23 loaded the highest on the first component, which was associated with increased bone marrow lesions (BMLs) and WOMAC dysfunction score. IL-10, -12 and GM-CSF loaded on the second component, which was associated with increased cartilage volume, and decreased effusion synovitis and WOMAC scores. Leptin, adipsin and CRP loaded on the third component, which was positively associated with WOMAC scores. Resistin loaded on the fourth component, which was associated with increased BMLs and cartilage defects. Apelin-36 and adiponectin loaded on the fifth component, which was associated with increased BMLs.

Conclusion

Various inflammatory and metabolic components were associated differently with joint symptoms and structural changes in knee OA, suggesting a complex inflammatory and metabolic interrelationship in the pathogenesis of knee OA.
Matrix Metalloproteinases Control Hemocyte Trafficking in Innate Immunity of Manduca sexta
Authors: Vishnuvardhan Smitha , Boe Jordan Paul , Greenlee Kendra J
Published: June 2021

Matrix metalloproteinases (MMPs) are a family of conserved, proteolytic enzymes. MMPs can degrade most extracellular matrix proteins. As such; they are key enzymes in remodeling processes, such as molting and metamorphosis. They are also known to be upregulated in many disease states, where they may cause tissue damage. Yet their presence may be beneficial, as their inhibition may result in worsening of symptoms or increased mortality. We tested the hypothesis that MMPs play a role in innate immunity in the tobacco hornworm caterpillar, Manduca sexta. We infected 5th instar caterpillars with E. coli DH5α in the presence or absence of the MMP inhibitor, GM6001. Larvae infected with E. coli DH5α had significantly more circulating hemocytes when compared to the larvae which received an MMP inhibitor, suggesting that MMPs may be important for hemocyte recruitment from the fat body. The majority of the circulating hemocytes were granulocytes, a cell type that phagocytoses forein bodies, including pathogens. In addition, we used flow cytometry to assess phagocytic ability. Hemocytes in the presence of the MMP inhibitor were less able to phagocytose sephadex beads, supporting the hypothesis that this MMP may contribute to cellular innate immune function.

This work was funded in part by NDSU, NSFEPSCoR #EPS‐00447679, and NIH 2P20RR015566.
Nursing Faculty Experiences During the COVID-19 Pandemic Response
Authors: Sacco Tara L. , Kelly Michelle M.
Published: June 2021

AIM

The specific aim of the study was to describe nursing faculty experiences during the COVID-19 pandemic.

BACKGROUND

Academic nursing experiences were disrupted due to the COVID-19 pandemic. There is concern that the resulting stress threatens nursing faculty emotional well-being.

METHOD

A descriptive, quantitative study was conducted, exploring faculty academic and clinical roles during the COVID-19 pandemic, including perception of institutional support provided; faculty burnout, satisfaction, and well-being; and student support needs and well-being.

RESULTS

Analyses were performed on 117 quantitative and 49 qualitative responses. Participants perceived support from academic institutions and increased need to provide emotional support to students. Most reported negative effects on well-being but did not report high levels of burnout.

CONCLUSION

Nursing faculty are essential to the profession. Stress responses from the COVID-19 pandemic may not be fully realized. Nursing faculty require proactive and sustained institutional and personal support to provide exceptional ongoing education, build resilience, and support students.
Comparing Mid-Term Outcomes Between ACDF and Minimally Invasive Posterior Cervical Foraminotomy in the Treatment of Cervical Radiculopathy
Authors: Emami Arash , Coban Daniel , Changoor Stuart , Dunn Conor , Sahai Nikhil , Sinha Kumar , Hwang Ki Soo , Faloon Michael
Published: June 2021

Study Design.

Retrospective cohort study.

Objective.

To compare minimally invasive posterior cervical foraminotomy (MI-PCF) and anterior cervical discectomy and fusion (ACDF) in the treatment of unilateral cervical radiculopathy.

Summary of Background Data.

MI-PCF has been shown to be equally effective as ACDF in treating cervical radiculopathy due to foraminal stenosis and similar pathologies. Additionally, it has been hypothesized that preserving motion and avoiding fusion reduces risk for adjacent segment disease, but potentially increases risk for subsequent revision to an ACDF. With similar short-term outcomes and substantial advantages, MI-PCF may be an effective alternative to ACDF for addressing appropriate cervical pathology.

Methods.

A retrospective review was performed to identify patients between 2009 and 2013 who underwent ACDF or MI-PCF with a minimum follow-up of 7 years. Demographic data was recorded. Revision rates and average time to revision between cohorts were compared. Clinical outcomes were assessed at each follow-up visit with Neck Disability Index and Visual Analog Scale for neck and Visual Analog Scale for arm pain scores. All complications were reviewed. Standard binomial and categorical comparative analysis were performed.

Results.

A total of 251 consecutive patients were included (205 ACDF, 46 MI-PCF). Mean follow-ups for the ACDF and MI-PCF groups were 98.3 and 95.9 months, respectively. Complication rates were 2.9% and 2.2% for the ACDF and MI-PCF cohorts, respectively (P = 0.779). Revision rates were 7.8% for the ACDF cohort and 8.7% for the MI-PCF cohort (P = 0.840). Both cohorts experienced significant improvements in their clinical scores compared with their preoperative values. Final Visual Analog Scale for neck pain (ACDF: 2.6; MI-PCF: 1.6) and Visual Analog Scale for arm pain (ACDF: 1.1; MI-PCF: 0.4) scores differed significantly at final follow-up (P =  < 0.001; P =  < 0.001).

Conclusion.

MI-PCF is a safe and effective alternative to ACDF in the treatment of cervical radiculopathy, demonstrating substantial benefit. After final follow-up, MI-PCF demonstrated superior improvements in Visual Analog Scale scores, without increased complication or revision rates.

Level of Evidence: 3
Long noncoding RNA ZFPM2-AS1 promotes the proliferation, migration, and invasion of hepatocellular carcinoma cells by regulating the miR-576-3p/HIF-1α axis
Authors: Song Yubao , Jin Xin , Liu Yong , Wang Shuiying , Bian Fang , Zhao Qingqing , Shi Hanping , Gao Zefeng
Published: June 2021

Long noncoding RNA (LncRNA) zinc finger protein multitype 2 antisense RNA 1 (ZFPM2-AS1) is highly expressed in a variety of tumors and is involved in promoting the malignant biological behaviors of cancer cells. However, the mechanism of ZFPM2-AS1 in the progression of hepatocellular carcinoma (HCC) remains to be explored. The ZFPM2-AS1 expression in HCC was measured by quantitative real-time PCR (qRT-PCR); cell counting kit-8, 5-bromo-2′-deoxyuridine (BrdU), and transwell assays were used to confirm the biological functions of ZFPM2-AS1 in regulating the malignant biological behaviors of HCC cells; the luciferase reporter gene assay was employed to detect whether ZFPM2-AS1 could bind to microRNA (miR)-576-3p; the regulatory relationship between ZFPM2-AS1 and miR-576-3p was probed by qRT-PCR; the effects of ZFPM2-AS1 and miR-576-3p on the expression of hypoxia-inducible factor 1α (HIF-1α) were detected by qRT-PCR and Western blot. The expression of ZFPM2-AS1 in HCC tissues, compared with that in normal liver tissues, was significantly upregulated. Knockdown of ZFPM2-AS1 markedly inhibited HCC cell proliferation, migration, and invasion while the overexpression of ZFPM2-AS1 worked oppositely. miR-576-3p could reverse the effects of ZFPM2-AS1 on the biological behaviors of HCC cells. Besides, ZFPM2-AS1 could bind to miR-576-3p and positively regulate the expression of HIF-1α, a target gene of miR-576-3p, by adsorbing miR-576-3p. ZFPM2-AS1 is abnormally highly expressed in HCC and facilitates proliferation, migration, and invasion of HCC cells by adsorbing miR-576-3p and upregulating HIF-1α expression.
Bradyrhizobium septentrionale sp. nov. (sv. septentrionale) and Bradyrhizobium quebecense sp. nov. (sv. septentrionale) associated with legumes native to Canada possess rearranged symbiosis genes and numerous insertion sequences
Authors: Bromfield Eden S. P. , Cloutier Sylvie
Published: June 2021

Six bacterial strains isolated from root nodules of soybean plants that had been inoculated with root-zone soil of legumes native to Canada were previously characterized and 1) placed in two novel lineages within the genus

Bradyrhizobium

and 2) assigned to symbiovar septentrionale. Here we verified the taxonomic status of these strains using genomic and phenotypic analyses. Phylogenetic analyses of five protein encoding partial gene sequences as well as 52 full length ribosome protein subunit gene sequences confirmed placement of the novel strains in two highly supported lineages distinct from named

Bradyrhizobium

species. The highest average nucleotide identity values of strains representing these two lineages relative to type strains of closest relatives were 90.7 and 92.3% which is well below the threshold value for bacterial species circumscription. The genomes of representative strains 1S1T, 162S2 and 66S1MBT have sizes of 10598256, 10733150 and 9032145 bp with DNA G+C contents of 63.5, 63.4 and 63.8 mol%, respectively. These strains possess between one and three plasmids based on copy number of plasmid replication and segregation (repABC) genes. Novel strains also possess numerous insertion sequences, and, relative to reference strain

Bradyrhizobium diazoefficiens

USDA110T, exhibit inversion and fragmentation of nodulation (nod) and nitrogen-fixation (nif) gene clusters. Phylogenetic analyses of nodC and nifH gene sequences confirmed placement of novel strains in a distinct lineage corresponding to symbiovar septentrionale. Data for morphological, physiological and symbiotic characteristics complement the sequence-based results. The data presented here support the description of two new species for which the names Bradyrhizobium septentrionale sp. nov. (sv. septentrionale) and Bradyrhizobium quebecense sp. nov. (sv. septentrionale) are proposed, with 1S1T (=LMG 29930T=HAMBI 3676T) and 66S1MBT (=LMG 31547T=HAMBI 3720T) as type strains, respectively.
Highly-specific memory B cells generation after the 2nd dose of BNT162b2 vaccine compensate for the decline of serum antibodies and absence of mucosal IgA
Authors: Mortari Eva Piano , Russo Cristina , Vinci Maria Rosaria , Terreri Sara , Salinas Ane Fernandez , Piccioni Livia , Alteri Claudia , Colagrossi Luna , Coltella Luana , Ranno Stefania , Linardos Giulia , Agosta Marilena , Albano Christian , Agrati Chiara , Castilletti Concetta , Meschi Silvia , Romania Paolo , Roscilli Giuseppe , Pavoni Emiliano , Camisa Vincenzo , Santoro Annapaola , Brugaletta Rita , Magnavita Nicola , Ruggiero Alessandra , Cotugno Nicola , Amodio Donato , Atti Marta Luisa Ciofi Degli , Giorgio Daniela , Russo Nicoletta , Salvatori Guglielmo , Corsetti Tiziana , Locatelli Franco , Perno Carlo Federico , Zaffina Salvatore , Carsetti Rita
Published: June 2021

Specific memory B cells and antibodies are reliable read-out of vaccine efficacy. We analyzed these biomarkers after one and two doses of BNT162b2 vaccine. The second dose significantly increases the level of highly-specific memory B cells and antibodies. Two months after the second dose, specific antibody levels decline, but highly specific memory B cells continue to increase thus predicting a sustained protection from COVID-19.

Graphical Abstract
Shrimp parvovirus circular DNA fragments arise from both endogenous viral elements (EVE) and the infecting virus
Authors: Taengchaiyaphum Suparat , Buathongkam Phasini , Sukthaworn Suchitraporn , Wongkhaluang Prapatsorn , Sritunyalucksana Kallaya , Flegel Timothy William
Published: June 2021

Some insects use endogenous reverse transcriptase (RT) to make variable viral copy DNA (vcDNA) fragments from viral RNA in linear (lvcDNA) and circular (cvcDNA) forms. The latter form is easy to extract selectively. The vcDNA produces small interfering RNA (siRNA) variants that inhibit viral replication via the RNA interference (RNAi) pathway. The vcDNA is also autonomously inserted into the host genome as endogenous viral elements (EVE) that can also result in RNAi. We hypothesized that similar mechanisms occurred in shrimp. We used the insect methods to extract circular viral copy DNA (cvcDNA) from the giant tiger shrimp (Penaeus monodon) infected with a virus originally named infectious hypodermal and hematopoietic necrosis virus (IHHNV). Simultaneous injection of the extracted cvcDNA plus IHHNV into whiteleg shrimp (Penaeus vannamei) resulted in a significant reduction in IHHNV replication when compared to shrimp injected with IHHNV only. Next generation sequencing (NGS) revealed that the extract contained a mixture of two general IHHNV-cvcDNA types. One showed 98 to 99% sequence identity to GenBank record AF218266 from an extant type of infectious IHHNV. The other type showed 98% sequence identity to GenBank record DQ228358, an EVE formerly called non-infectious IHHNV. The startling discovery that EVE could also give rise to cvcDNA revealed that cvcDNA provided an easy means to identify and characterize EVE in shrimp and perhaps other organisms. These studies open the way for identification, characterization and use of protective cvcDNA as a potential shrimp vaccine and as a tool to identify, characterize and select naturally protective EVE to improve shrimp tolerance to homologous viruses in breeding programs.