bluuebunny/crossref_metadata_2025 huggingface dataset:
Whole‐genome sequencing reveals asymmetric introgression between two sister species of cold‐resistant leaf beetles
Authors: Lukicheva Svitlana , Mardulyn Patrick
Published: June 2021

A large number of genetic variation studies have identified cases of mitochondrial genome introgression in animals, indicating that reproductive barriers among closely related species are often permeable. Because of its sheer size, the impact of hybridization on the evolution of the nuclear genome is more difficult to apprehend. Only a few studies have explored it recently thanks to recent progress in DNA sequencing and genome assembly. Here, we analysed whole‐genome sequence variation among multiple individuals of two sister species of leaf beetles inside their hybrid zone, in which asymmetric mitochondrial genome introgression had previously been established. We used a machine learning approach based on computer simulations for training to identify regions of the nuclear genome that were introgressed. We inferred asymmetric introgression of ≈2% of the genome, in the same direction that was observed for the mitochondrial genome. Because a previous study based on a reduced‐representation sequencing approach was not able to detect this introgression, we conclude that whole‐genome sequencing is necessary when the fraction of the introgressed genome is small. We also analysed the whole‐genome sequence of a hybrid individual, demonstrating that hybrids have the capacity to backcross with the species for which virtually no introgression was observed. Our data suggest that one species has recently invaded the range of the other and/or some alleles that where transferred from the invaded into the invading species could be under positive selection and may have favoured the adaptation of the invading species to the Alpine environment.
DNA damage checkpoint activation affects peptidoglycan synthesis and late divisome components in Bacillus subtilis
Authors: Masser Emily A. , Burby Peter E. , Hawkins Wayne D. , Gustafson Brooke R. , Lenhart Justin S. , Simmons Lyle A.
Published: June 2021

During normal DNA replication, all cells encounter damage to their genetic material. As a result, organisms have developed response pathways that provide time for the cell to complete DNA repair before cell division occurs. In Bacillus subtilis, it is well established that the SOS‐induced cell division inhibitor YneA blocks cell division after genotoxic stress; however, it remains unclear how YneA enforces the checkpoint. Here, we identify mutations that disrupt YneA activity and mutations that are refractory to the YneA‐induced checkpoint. We find that YneA C‐terminal truncation mutants and point mutants in or near the LysM peptidoglycan binding domain render YneA incapable of checkpoint enforcement. In addition, we develop a genetic method which isolated mutations in the ftsW gene that completely bypassed checkpoint enforcement while also finding that YneA interacts with late divisome components FtsL, Pbp2b, and Pbp1. Characterization of an FtsW variant resulted in considerably shorter cells during the DNA damage response indicative of hyperactive initiation of cell division and bypass of the YneA‐enforced DNA damage checkpoint. With our results, we present a model where YneA inhibits septal cell wall synthesis by binding peptidoglycan and interfering with interaction between late arriving divisome components causing DNA damage checkpoint activation.
Bacterial lysate treatment in allergic disease: A systematic review and meta‐analysis
Authors: Li Chengmei , Zhou Hua , Zhang Wei , Che Datian
Published: June 2021

Objective

The aim of this review was to assess the efficacy of bacterial lysate treatment in patients with allergic disease.

Method

Randomized controlled trials (RCTs) of bacterial lysate therapy for patients with allergic diseases (asthma, atopic dermatitis, and allergic rhinitis) were searched using PubMed, EMBASE, Cochrane, China National Knowledge Infrastructure, Chinese Biomedical literature, and Wanfang databases up to March 2020. Based on the guidelines of the Cochrane collaboration, risk of bias was assessed.

Results

This meta‐analysis based on 19 studies comparing bacterial lysate‐treated patients with a control group showed a 24% (RR: 1.24, 95% CI [1.19, 1.30]) increase in improvement of allergy symptom control. In addition, the improvement of asthma symptom control was 22% (RR: 1.22, 95% CI [1.14, 1.26]) higher in the bacterial lysate treatment group. Moreover, the levels of immunoglobulin (IgA and IgG), T lymphocyte subtype (CD3+, CD4+, CD4+/CD8+, Th1), and cytokines (IFN‐γ, IL‐2, and IL‐12) were increased in the treated group compared with controls. There was no significant difference in adverse event rate between the two groups.

Conclusion

Treatment with bacterial lysate improves symptom control in patients with allergic diseases on the basis of routine therapy. No adverse risk was found in this meta‐analysis.
Calmodulin‐binding transcription activator AtSR1/CAMTA3 fine‐tunes plant immune response by transcriptional regulation of the salicylate receptor NPR1
Authors: Yuan Peiguo , Tanaka Kiwamu , Poovaiah B. W.
Published: June 2021

Calcium (Ca2+) signalling regulates salicylic acid (SA)‐mediated immune response through calmodulin‐meditated transcriptional activators, AtSRs/CAMTAs, but its mechanism is not fully understood. Here, we report an AtSR1/CAMTA3‐mediated regulatory mechanism involving the expression of the SA receptor, NPR1. Results indicate that the transcriptional expression of NPR1 was regulated by AtSR1 binding to a CGCG box in the NPR1 promotor. The atsr1 mutant exhibited resistance to the virulent strain of Pseudomonas syringae pv. tomato (Pst), however, was susceptible to an avirulent Pst strain carrying avrRpt2, due to the failure of the induction of hypersensitive responses. These resistant/susceptible phenotypes in the atsr1 mutant were reversed in the npr1 mutant background, suggesting that AtSR1 regulates NPR1 as a downstream target during plant immune response. The virulent Pst strain triggered a transient elevation in intracellular Ca2+ concentration, whereas the avirulent Pst strain triggered a prolonged change. The distinct Ca2+ signatures were decoded into the regulation of NPR1 expression through AtSR1's IQ motif binding with Ca2+‐free‐CaM2, while AtSR1's calmodulin‐binding domain with Ca2+‐bound‐CaM2. These observations reveal a role for AtSR1 as a Ca2+‐mediated transcription regulator in controlling the NPR1‐mediated plant immune response.
Cooperative Advertising in a Dynamic Three‐Echelon Supply Chain
Authors: Kennedy Adrian Patrick , Sethi Suresh P. , Siu Chi Chung , Yam Sheung Chi Phillip
Published: June 2021

We propose a model to assess the value of a distributor in a dynamic stochastic cooperative advertising supply chain in which a manufacturer wholesales its product to a distributor who in turn sells it to a retailer. Moreover and importantly, the distributor also intermediates the pricing and advertising decisions between the manufacturer and the retailer. For the resulting three‐player hierarchical game formulation of the supply chain, we characterize the feedback Stackelberg equilibrium in terms of a system of coupled algebraic equations and show it to admit a unique solution. We find that the value added by the distributor to the supply chain depends critically on the nature of the demand function for the product, a result that has practical implications for the kinds of product where having a distributor is most desirable. Second, our model indicates that the presence of the distributor can enhance the margins of both the retailer and the manufacturer relative to the case of no distributor, and provide explicit conditions for this to occur. Third, we present numerical analysis that indicates that if the distributor generates sufficiently large transportation cost savings, then the three‐echelon supply chain can lead in the long run to higher market awareness, lower advertising expenditure, and higher value extracted, relative to the two‐echelon model. Finally, in addition to retailer advertising that is subsidized by the manufacturer, we also provide the manufacturer an option to do national advertising and show its viability.
An effectively causal deep learning algorithm to increase intelligibility in untrained noises for hearing-impaired listeners
Authors: Healy Eric W. , Tan Ke , Johnson Eric M. , Wang DeLiang
Published: June 2021

Real-time operation is critical for noise reduction in hearing technology. The essential requirement of real-time operation is causality—that an algorithm does not use future time-frame information and, instead, completes its operation by the end of the current time frame. This requirement is extended currently through the concept of “effectively causal,” in which future time-frame information within the brief delay tolerance of the human speech-perception mechanism is used. Effectively causal deep learning was used to separate speech from background noise and improve intelligibility for hearing-impaired listeners. A single-microphone, gated convolutional recurrent network was used to perform complex spectral mapping. By estimating both the real and imaginary parts of the noise-free speech, both the magnitude and phase of the estimated noise-free speech were obtained. The deep neural network was trained using a large set of noises and tested using complex noises not employed during training. Significant algorithm benefit was observed in every condition, which was largest for those with the greatest hearing loss. Allowable delays across different communication settings are reviewed and assessed. The current work demonstrates that effectively causal deep learning can significantly improve intelligibility for one of the largest populations of need in challenging conditions involving untrained background noises.
Amplification of the amoA Gene from Diverse Species of Ammonium-Oxidizing Bacteria and from an Indigenous Bacterial Population from Seawater
Authors: Sinigalliano C D , Kuhn D N , Jones R D
Published: June 2021

Vol. 61, no. 7, p. 2705, column 2, lines 9 to 16: these sentences should read as follows. "These two sequences show 75% identity at the DNA level to the published N. europaea sequence and show 85% identity to each other. Interestingly, the regions that our primers were designed to target show 5 and 3 mismatches with the Nitrosospira sequence and 2 and 2 mismatches with the Nitrosolobus sequence for the forward and reverse primers, respectively." [This corrects the article on p. 2702 in vol. 61.].
Immune responses to Rickettsia akari infection in congenitally athymic nude mice
Authors: Kenyon R H , Pedersen C E
Published: June 2021

Athymic BALB/c nude mice and euthymic BALB/c mice were infected with Rickettsia akari by the intraperitoneal route. The rickettsialpox infection was terminated in euthymic mice with only two intraperitoneal injections of the antibiotic oxytetracycline, whereas prolonged treatment was necessary to terminate the infection in athymic mice. Both athymic and euthymic mice produced specific antibody, but athymic mice were still susceptible to reinfection. Killed R. akari served as a protective immunogen in euthymic, but no in athymic, mice. When spleen cells from convalescent euthymic mice were transferred to syngeneic athymic mice, recipients showed protection against challenge. This suggests that a T-cell-dependent step is generally necessary to terminate the rickettsialpox infection.
Bactericidal mechanisms of human breast milk leukocytes
Authors: Johnson D F , France G L , Marmer D J , Steele R W
Published: June 2021

The functional capacity of human breast milk phagocytes was evaluated with both bactericidal and biochemical assays. Acridine orange was used as a vital stain for bacteria to directly visualize phagocytosis and killing. Bactericidal capabilities were further examined by colony count and chemiluminescent methods. Cytocentrifuged specimens stained for myeloperoxidase exhibited enzyme activity in breast milk leukocytes equal to that of peripheral neutrophils. A radioisotopic assay of hexose monophosphate shunt activity demonstrated metabolic activity in breast milk leukocytes greater than that in peripheral blood neutrophils. However, the chemiluminescent response of breast cells was negligible, apparently the result of quenching secondary to fat present in the milk; preincubation of human blood leukocytes with the fatty layer of breast milk produced similar inhibition in the chemiluminescence assay. By most parameters breast milk phagocytes are at least equal to blood neutrophils.
Effect of surface modifiers on an ectoenzyme: granulocyte 5'-nucleotidase
Authors: Smolen J E , Karnovsky M L
Published: June 2021

Several agents that react with plasma membranes, namely the native lectins concanavalin A, Ricinus communis agglutinin, and wheat germ agglutinin, the modified lectin succinyl concanavalin A, and sodium meta-periodate, inhibited the ecto-5'-nucleotidase of intact guinea pig granulocytes. Stimulation of the enzyme was not observed at any lectin concentration. Inhibition by native lectins could be blocked or reversed by appropriate competing hapten sugars. In the case of concanavalin A, reversal could be achieved at 37 degrees C, but not at 5 degrees C. When lectins were used in combination with each other, the effects were found to be largely independent. However, when concanavalin A and R. communis agglutinin were applied together, complications arose because the former lectin binds to the latter as well as to the cell surface. To avoid some of the complexities inherent in studying intact cell 5'-nucleotidase and to gain additional information about the system, two broken cell enzyme preparations were also examined. The enzyme of plasma membrane-enriched fractions was inhibited by all five agents mentioned above. 5'-Nucleotidase solubilized in sodium deoxycholate was inhibited by the four lectins but stimulated by periodate. The effects of the surface modifiers on kinetic data for all three enzyme preparations are consistent with the hypothesis that direct interactions with the enzyme molecule give rise to changes in Vmax; interactions at membrane sites other than 5'-nucleotidase itself could cause increases in apparent Km values. Effects of interactions of ectoenzymes with plant lectins may serve as models for phenomena that result from cell-cell interactions or from interactions of animal cells with lectin-like components of the cellular environment.
Alterations in the Distribution and Proliferative Responses of Rhesus Monkey Peripheral Blood and Spleen Cells During Malaria (
Plasmodium knowlesi
) Infection
Authors: Taylor Diane W. , Crum Suzanne Richmond , Kramer Kenton J. , Siddiqui Wasim A.
Published: June 2021

Rhesus monkeys are used frequently as animal models in malaria research, but few studies have evaluated lymphocyte functions in these animals after experimental infections with the primate malarial parasite
Plasmodium knowlesi.
In this study, the distribution and mitogen responses of mononuclear cells in the peripheral blood and spleens of 16
P. knowlesi
-infected rhesus monkeys were followed. All animals included in the study developed acute infections and were bled out with parasitemias of more than 50%. With progression of the infection, alterations in the peripheral blood mononuclear cells were observed, including decreases in the percentage of T cells (measured by E rosette formation) and the total numbers of E and EAC rosette-forming cells per cubic millimeter. In addition, peripheral blood mononuclear cells displayed reduced responses to mitogen stimulation with phytohemagglutinin, concanavalin A, and pokeweed mitogen. Peripheral blood mononuclear cells from infected animals showed similar reductions in mitogen responses when cultured in media containing 15% autologous pre- or postinfection plasma. The mitogen responses of spleen cells did not appear to be affected, but a significant reduction in the proportion of splenic T cells was observed. These lymphocyte changes in
P. knowlesi
-infected rhesus monkeys are similar to those reported for mice with acute rodent malaria and for humans with chronic
Plasmodium falciparum
infections.
Participation of normal human immunoglobulins M, G, and A in opsonophagocytosis and intracellular killing of Bacteroides fragilis and Bacteroides thetaiotaomicron by human polymorphonuclear leukocytes
Authors: Bjornson A B , Bjornson H S , Kitko B P
Published: June 2021

Restoration of the ability of hypogammaglobulinemic serum to support opsonophagocytosis and intracellular killing of Bacteroides fragilis and Bacteroides thetaiotaomicron by human polymorphonuclear leukocytes was achieved by supplementation with normal human immunoglobulin M, but not with normal human immunoglobulin G. Polymorphonuclear leukocyte bactericidal activity in the presence of immunoglobulin A-deficient human serum was equivalent to that observed in the presence of normal human serum.
Increased toxicity of endotoxin for tumor-bearing mice and mice responding to bacterial pathogens: macrophage activation as a common denominator
Authors: Berendt M J , Newborg M F , North R J
Published: June 2021

Mice bearing the syngeneic SA-1 sarcoma or treated with live Mycobacterium bovis BCG or Formalin-killed Corynebacterium parvum acquired a greatly increased susceptibility to the lethal effects of endotoxin. In all three experimental models, the acquisition of increased sensitivity to endotoxin was concordant with the generation of a systemically activated macrophage system.
Fungicidal activity of rabbit alveolar and peritoneal macrophages against Candida albicans
Authors: Lehrer R I , Ferrari L G , Patterson-Delafield J , Sorrell T
Published: June 2021

We tested the ability of rabbit macrophages to kill Candida albicans in vitro. Resident (unstimulated) alveolar macrophages killed 28.1 +/- 1.9% of ingested organisms in 4 h, whereas resident peritoneal macrophages killed only 15.2 +/- 1.3% (mean +/- standard error of the mean, P < 0.01). Peritoneal macrophages obtained from rabbits treated 3 weeks earlier with complete Freund adjuvant showed enhanced candidacidal activity relative to normally resident peritoneal cells (28.2 +/- 3.1%, P < 0.01). Candidacidal activity by alveolar macrophages recovered from such treated animals was slightly enhanced relative to untreated alveolar macrophages (32.9 +/- 2.3%). Candidacidal activity by peritoneal and alveolar macrophages was not decreased by several agents (cyanide, azide, sulfadiazine, and phenylbutazone) that inhibit the ability of human blood monocytes to kill C. albicans. In contrast, candidacidal activity by alveolar macrophages was greatly diminished by iodoacetate, an ineffective inhibitor of this function in human monocytes. We conclude that rabbit macrophages kill C. albicans by a fungicidal mechanism distinct from the peroxidase-H2O2 mechanism of human granulocytes and monocytes, and that the fungicidal properties of peritoneal and alveolar macrophage populations are enhanced after nonspecific stimulation with complete Freund adjuvant.
In vitro inhibition of Neisseria gonorrhoeae growth by strict anaerobes
Authors: Morin A , Saheb S A , Bisaillon J G , Beaudet R , Sylvestre M
Published: June 2021

Thirty two anaerobic bacterial strains were screened for their in vitro inhibitory activity toward 21 Neisseria gonorrhoeae strains, including two penicillin-resistant strains. From this screening, six anaerobic bacteria belonging to the genera Bacteroides, Peptostreptococcus, and Eubacterium were selected for their large antigonococcal spectrum of activity. The inhibitory activity of these six strains appears to be specific to the gonococcus as a variety of anaerobes and aerobes were not generally inhibited by these strains. The antigonococcal effect was not due to pH change or nutrient depletion of the media.
Anti-immunoglobulins and heterophil agglutinins in experimental trypanosomiasis
Authors: Mattern P , Klein F , Pautrizel R , Jongepier-Geerdes Y E
Published: June 2021

Rheumatoid factor (RF)-like substances and heterophil agglutinins (HA) were induced in rabbits by infection with a strain of Trypanosoma equiperdum. Infection with a T. gambiense strain produced HA, but no RF. RFs appeared usually before immunoglobulin G (IgG) levels started to increase. They disappeared spontaneously after 4 to 6 weeks. HA were of the IgM class, appeared within 1 to 2 weeks after infection, and usually remained at high levels afterwards. They could not be absorbed out with lyophilized whole trypanosomes. Therapy suppressed the formation of RF as well as of HA, but IgG complexes as well as antibodies against trypanosomal antigens remained present for considerable periods after the installment of therapy. It is concluded that RFs are not induced by IgG complexes. The results suggest that HA are probably not cross-reacting antibodies induced by trypanosomal antigens.
Bactericidal activity of human serum against Escherichia coli chi1776
Authors: Alexander W J , Alexander L S , Curtiss R
Published: June 2021

Escherichia coli chi1776 is a host strain providing the EK2 level of biological containment. Laboratories equipped to use this strain may be located near medical care facilities where patients prone to infection may be found. We have therefore documented the marked susceptibility of chi1776 to killing by human serum from normal as well as ill individuals.
In Vitro Adhesion of Uropathogenic
Escherichia coli
to Human Periurethral Cells
Authors: Källenius Gunilla , Möllby Roland , Winberg Jan
Published: June 2021

The in vitro adhesion of three uropathogenic strains of
Escherichia coli
to epithelial cells from the periurethral area (area surrounding the urethral orifice) of women with and without a history of recurrent urinary tract infections was investigated. All strains showed a specific mannose-resistant hemagglutination restricted to human erythrocytes. Since only a few hundred periurethral cells were used in each test, gentle methods were required. Optimal results were obtained with bacteria grown for 16 h at 37°C in nutrient broth without shaking. The binding of bacteria seemed to be irreversible under the conditions studied, since repeated washings of the epithelial cells after incubation did not decrease the number of adhering bacteria. Chloramphenicol was used to control the number of added bacteria in the incubation system. A difference in the adhesive capacity of periurethral cells of infection-prone and healthy individuals was most evident at concentrations of 2.5 × 10
9
bacteria/ml. Electron microscope studies indicated that pili mediated the adhesion. Adhesion was correlated with the mannose-resistant hemagglutination of human erythrocytes, indicating that the pili were not type 1 pili. Day-to-day variations in the adhesiveness of the bacteria were reduced by selecting well-adhering bacteria with the aid of in vitro passage on periurethral cells or human erythrocytes, and by exclusion of bacteria with low hemagglutination ability.
A Discussion Group Program Enhances the Conceptual Reasoning Skills of Students Enrolled in a Large Lecture-Format Introductory Biology Course
Authors: Peteroy-Kelly Marcy A.
Published: June 2021

It has been well-established that discussion groups enhance student learning in large lecture courses. The goal of this study was to determine the impact of a discussion group program on the development of conceptual reasoning skills of students enrolled in a large lecture-format introductory biology course. In the discussion group, students worked on problems based on topics discussed in lecture. The program was evaluated using three assessment tools. First, student responses to pre- and posttests were analyzed. The test question asked the students to demonstrate the relationships between 10 different but related terms. Use of a concept map to link the terms indicated an advanced level of conceptual reasoning skills. There was a 13.8% increase in the use of concept maps from pre- to posttest. Second, the students took a Likert-type survey to determine the perceived impact of the program on their conceptual reasoning skills. Many of the students felt that the program helped them understand and use the main course concepts to logically solve problems. Finally, average exam grades increased as the semester progressed. The average final grade in the course was 75%. Students enrolled in the course the previous year (where the lecture component of the course did not assess or reflect student learning in the discussion group) had an average final grade of 69%. The results of this study demonstrate that the discussion group program improves the conceptual reasoning skills of students enrolled in a large lecture-format introductory biology course.
Amino acid alterations within a highly conserved region of the Rous sarcoma virus src gene product pp60src inactivate tyrosine protein kinase activity
Authors: Bryant D L , Parsons J T
Published: June 2021

Bisulfite mutagenesis techniques have been used to introduce single-point mutations within a region of the Rous sarcoma virus src gene defined by a BglI restriction endonuclease cleavage site. The mutants of Rous sarcoma virus that are produced by these techniques encode src proteins which contain single amino acid changes within a highly conserved amino acid sequence encompassing residues 430 to 433. DNA from the mutants CHpm26 ( Ala430 to Val), CHpm9 ( Pro431 to Ser), CHpm6 ( Glu432 to Lys), and CHpm65 ( Ala433 to Thr) each failed to transform chicken cells upon transfection, whereas DNA from CHpm59 (a third base alteration in the codon for Glu432 ) readily transformed chicken cells. Analysis of immune complexes containing the altered src proteins indicates that these proteins have decreased tyrosine protein kinase activity in vitro. In vivo labeling of cells infected with the mutant virus revealed diminished levels of the tyrosine-phosphorylated 34,000-molecular-weight protein. These data indicate that mutations within the sequence Ala430 - Pro431 - Glu432 - Ala433 lead to alterations in pp60src-specific tyrosine protein kinase activity and a concomitant loss of transforming potential of the mutant virus.
Acute arthritis, skin rash and Lofgren’s syndrome
Authors: Chauhan Ajay , Jandial Aditya , Mishra Kundan , Sandal Rajeev
Published: June 2021

Sarcoidosis is an autoimmune multisystem granulomatous disorder of unknown aetiology, which mainly affects the adults in the age group of 20–39 years. The disease can affect any organ in the body but mainly presents as bilateral hilar lymphadenopathy, pulmonary infiltrates, cutaneous lesions, ocular manifestations and arthropathy. Lofgren’s syndrome is an uncommon initial presentation of sarcoidosis which is recognised by the classical triad of acute arthritis, erythema nodosum and bilateral hilar lymphadenopathy. We describe a newly diagnosed case of sarcoidosis who presented as Lofgren’s syndrome. Acute sarcoid arthritis should be kept as one of the differential diagnoses for patients presenting with acute arthritis and skin lesions; and chest X-ray should be considered to rule out bilateral hilar lymphadenopathy in these patients. Early suspicion and identification of classical clinical features are essential to establish early diagnosis.
Two cases of secondary AA amyloidosis involving the skin and chronic kidney infection with a nephrotic syndrome in a high-income country
Authors: Garo Florian , Chatelain Juliette , Aglae Cedric , Moranne Olivier
Published: June 2021

We present two French cases of amyloid-associated (AA) amyloidosis secondary to chronic infections. Patient 1, a 51-year-old heroin addict, was hospitalised for chest pain and anasarca. During hospitalisation, a nephrotic syndrome with an inflammatory condition was discovered along with a chronic skin ulcer on his arm. Salivary gland and kidney biopsies confirmed the diagnosis of AA amyloidosis. Renal function quickly declined and haemodialysis was initiated 6 months later. Patient 2, a 55-year-old woman, was hospitalised for obstructive pyelonephritis secondary to coraliform lithiasis. Renal insufficiency with an impure nephrotic syndrome was found. After nephrectomy due to chronic pyelonephritis and an atrophic cortex on the abdominal scan, the histology revealed AA amyloidosis. Despite treatment with ACE inhibitors and control of inflammation, the nephrotic syndrome persisted with rapid decline of the kidney function.
Mosaic de novo SNRPN gene variant associated with Prader-Willi syndrome
Authors: Huang Yue , Grand Katheryn , Kimonis Virginia , Butler Merlin G , Jain Suparna , Huang Alden Yen-Wen , Martinez-Agosto Julian A , Nelson Stanley F , Sanchez-Lara Pedro A
Published: June 2021

Background

Prader-Willi syndrome (PWS) is an imprinting disorder caused by the absence of paternal expressed genes in the Prader-Willi critical region (PWCR) on chromosome 15q11.2-q13. Three molecular mechanisms have been known to cause PWS, including a deletion in the PWCR, uniparental disomy 15 and imprinting defects.

Results

We report the first case of PWS associated with a single-nucleotide SNRPN variant in a 10-year-old girl presenting with clinical features consistent with PWS, including infantile hypotonia and feeding difficulty, developmental delay with cognitive impairment, excessive eating with central obesity, sleep disturbances, skin picking and related behaviour issues. Whole-exome sequencing revealed a de novo mosaic nonsense variant of the SNRPN gene (c.73C>T, p.R25X) in 10% of DNA isolated from buccal cells and 19% of DNA from patient-derived lymphoblast cells. DNA methylation study did not detect an abnormal methylation pattern in the SNRPN locus. Parental origin studies showed a paternal source of an intronic single-nucleotide polymorphism within the locus in proximity to the SNRPN variant.

Conclusions

This is the first report that provides evidence of a de novo point mutation of paternal origin in SNRPN as a new disease-causing mechanism for PWS. This finding suggests that gene sequencing should be considered as part of the diagnostic workup in patients with clinical suspicion of PWS.
Promoting equity with a multi-principle framework to allocate scarce ICU resources
Authors: White Douglas , Lo Bernard
Published: June 2021

We wholeheartedly agree with Schmidt and colleagues’ efforts to promote equity in intensive care unit (ICU) triage. We also take issue with their characterisation of the New Jersey (NJ) allocation framework for ICU beds and ventilators, which is modelled after the multi-principle allocation framework we developed early in the pandemic. They characterise it as a two-criterion allocation framework and claim—without evidence—that it will ‘compound disadvantage for black patients’. However, the NJ triage framework—like the model allocation policy we developed—actually contains four allocation criteria: the two criteria that the authors mentioned (chances for survival and near-term prognosis) and two criteria that they failed to mention which we included to promote equity: giving priority to frontline essential workers and giving priority to younger patients. These omissions are problematic both for reasons of factual accuracy and because the two criteria they failed to acknowledge would likely mitigate rather than exacerbate racial disparities during triage.
Trends in e-cigarette brands, devices and the nicotine profile of products used by youth in England, Canada and the USA: 2017–2019
Authors: Hammond David , Reid Jessica L , Burkhalter Robin , O'Connor Richard J , Goniewicz Maciej L , Wackowski Olivia A , Thrasher James F , Hitchman Sara C
Published: June 2021

Background

The e-cigarette market has rapidly evolved, with a shift towards higher nicotine concentration and salt-based products, such asJUUL; however, the implications for youth vaping remain unclear.

Methods

Repeat cross-sectional online surveys were conducted in 2017, 2018 and 2019, with national samples of youth aged 16–19 years recruited from commercial panels in Canada (n=12 018), England (n=11 362) and the USA (n=12 110). Regression models examined differences between countries and over time in the types of e-cigarette products used (design and nicotine content), reasons for using brands and differences in patterns of use, sociodemographics and dependence symptoms by brand/nicotine content.

Results

In 2019, the use of pod- or cartridge-style e-cigarettes was greater in Canada and the USA than England, withSmokandJUULthe leading brands in all countries. In 2019, youth vapers in England were less likely to report using e-cigarettes with ≥2% nicotine (12.8%) compared with Canada (40.5%; adjusted OR (AOR)=4.96; 95% CI 3.51 to 7.01) and the USA (37.0%; AOR=3.99, 95% CI 2.79 to 5.71) and less likely to report using nicotine salt-based products (12.3%) compared with Canada (27.1%; AOR=2.77, 95% CI 1.93 to 3.99) and the USA (21.9%; AOR=2.00, 95% CI 1.36 to 2.95). In 2019, self-reported use of products with higher nicotine concentration was associated with significantly greater frequency of vaping, urges to vape and perceived vaping addiction (p<0.05 for all).

Conclusions

The use of high-nicotine salt-based products is associated with greater symptoms of dependence, includingJUULand other higher-nicotine brands. Greater use of high-nicotine salt-based products may account for recent increases in the frequency of vaping among youth in Canada and the USA.
Detection of bladder trabeculation by voiding cystourethrography and sonography: observations in boys with posterior urethral valves
Authors: Thüminger Jonas , Haid Bernhard , Oswald Josef
Published: June 2021

Background

As trabeculated bladder wall is often referred to as a sign of chronically increased intravesical pressure, we investigated whether voiding cystourethrography (VCUG) or sonography reliably predicts bladder trabeculation on later urethrocystoscopy.

Methods

A total of 76 consecutive patients (2012–2017) with cystoscopically confirmed posterior urethral valves (PUV) and pre-endoscopy VCUG were included. Sonography data were available for 68 of these patients. Radiological findings were reassessed and compared with endoscopic findings using Fisher’s exact test and Spearman’s rank assessment.

Results

VCUG showed a sensitivity of 83.3% and a specificity of 30% in predicting trabeculation on a later urethrocystoscopy, with no significant difference in determining mild or severe forms (p=0.51). Sonography proved a sensitivity of 27.6% and a specificity of 70%, with no correlation between sonographic signs and trabeculation on cystoscopy (r=0.1311). In addition, vesicoureteral reflux had no significant influence as a possible pressure pop-off mechanism on the development of trabeculation in our group.

Conclusions

While VCUG predicts bladder trabeculation in children with PUV with limited reliability, sonography mostly fails to detect trabeculation. Therefore, such findings should only be used with utmost caution in relation to clinical decision-making.
Space use of juvenile and subadult yellow perch (Perca flavescens) in the Detroit River using acoustic telemetry: incorporating variable detection ranges in vegetated areas
Authors: Matley Jordan K. , Klinard Natalie V. , Larocque Sarah M. , Weinz Amy A. , Colborne Scott F.
Published: June 2021

Understanding the space use of fishes in early life stages provides information that can contribute to effective fisheries management; however, it can be difficult to track fish in shallow, densely vegetated areas. Using acoustic telemetry, 60 subadult yellow perch (Perca flavescens) were tagged and monitored in a vegetated area of the Detroit River (May–November 2018). Variable detection range from submerged aquatic vegetation (SAV) was incorporated in estimates by applying a spatiotemporal correction to aid with interpretation of seasonal changes in activity space. Although subadult yellow perch were commonly detected in the array, demonstrating the importance of SAV habitat (mean detection residency index: 0.85), 60% of individuals were not detected following August, the period with highest activity space estimates, likely due to seasonal movements and predation. Individuals were more commonly detected during the daylight hours compared to night, but activity peaked at crepuscular periods. This study provided spatial information about the often-overlooked early life history of yellow perch, increasing the ecological information available for a species of management and conservation interest in the Great Lakes.
Acoustic emission techniques for the detection of simulated failures in historical vehicles engines
Authors: Brambilla Laura , Chalançon Brice , Roda Buch Alejandro , Cornet Emilie , Rapp Guillaume , Mischler Stefano
Published: June 2021

Technical and industrial heritage artefacts are characterized by the presence of mechanisms. The possibility to activate, or reactivate, these mechanisms is an integral part of the cultural values of this kind of patrimony. The artefacts’ functionality, however, requires an effective diagnostic in order to detect the onset of malfunctioning at a very early stage to avoid wear and breakdowns. The assessment of moving mechanisms of heritage objects may be performed using non-destructive methods, such as acoustic emission (AE). The ACUME_HV project aimed at developing diagnostic and monitoring protocols for historical vehicles’ engines using AE techniques. The case studies were performed on 2-cylinders Renault AG1 vehicles (collection of the “Musée National de l’Automobile – Collection Schlumpf” of Mulhouse, France). These cars are maintained in working conditions, and their engines are started periodically. After a first phase consisting in recording the reference signals of the selected engines, the project focused on detecting faults simulated on purpose, the latter reproducing common failures occurring in historical vehicles' engines.
CB1Rs in VMH neurons regulate glucose homeostasis but not body weight
Authors: Castorena Carlos M. , Caron Alexandre , Michael Natalie J. , Ahmed Newaz I. , Arnold Amanda G. , Lee Jiwon , Lee Charlotte , Limboy Chelsea , Tinajero Arely Salazar , Granier Madison , Wang Simeng , Horton Jay D. , Holland William L. , Lee Syann , Liu Chen , Fujikawa Teppei , Elmquist Joel K.
Published: June 2021

Cannabinoid 1 receptors (CB1Rs) regulate metabolic homeostasis, and CB1R inverse agonists reduce body weight and improve parameters of glucose metabolism. However, the cell populations expressing CB1Rs that regulate metabolic homeostasis remain unclear. CB1Rs are highly expressed in the ventromedial hypothalamic nucleus (VMH), which is a crucial node that regulates metabolism. With CRISPR/Cas9, we generated mice lacking CB1Rs specifically in VMH neurons and found that CB1Rs in VMH neurons are essential for the regulation of glucose metabolism independent of body weight regulation.
Circulating extracellular DNA is in association with continuous metabolic syndrome score in healthy adolescents
Authors: Celec Peter , Janovičová Ĺubica , Gurecká Radana , Koborová Ivana , Gardlík Roman , Šebeková Katarína
Published: June 2021

Obesity is associated with chronic low-grade inflammation that eventually leads to metabolic complications. Extracellular DNA (ecDNA) is a damage-associated molecular pattern. Extracellular mitochondrial DNA can activate innate immunity. We hypothesized that ecDNA, especially of mitochondrial origin, could be associated with components of the metabolic syndrome in young healthy probands. In a cross-sectional study, healthy adolescents ( n = 1,249) provided blood samples. Anthropometric data, blood pressure, and blood counts were assessed. In addition, biochemical analysis of sera or plasma was conducted, including the quantification of advanced oxidation protein products (AOPPs) as a marker of oxidative stress induced by neutrophil or monocyte activation. Plasma ecDNA was isolated and measured by fluorometry. Nuclear and mitochondrial DNA were quantified by real-time PCR. Males had higher total plasma ecDNA [15 (11–21) vs. 11 (8–17) ng/mL; median (interquartile range)], nuclear [1,760 (956–3,273) vs. 1,153 (600–2,292) genome equivalents (GE)/mL], and mitochondrial [37,181 (14,836–90,896) vs. 30,089 (12,587–72,286) GE/mL] DNA. ecDNA correlated positively with the continuous metabolic syndrome score ( r = 0.158 for males and r = 0.134 for females). Stronger correlations were found between ecDNA of mitochondrial origin and AOPP ( r = 0.202 and 0.186 for males and females, respectively). Multivariate regression analysis revealed associations of nuclear DNA with leukocyte and erythrocyte counts. The results of this study of healthy adolescents show that circulating ecDNA is associated with the risk of metabolic syndrome, not with obesity per se. The association between mitochondrial ecDNA and AOPP requires further attention as it supports a potential role of mitochondria-induced sterile inflammation in the pathogenesis of the metabolic syndrome.
Preliminary Study on the In Vitro Antitumor Effects of Nidus Vespae on Gastric Cancer
Authors: Zhu Ming , Han Weiwei , Ling Yang , Qi Qiufeng , Zhang Yaping , Peng Yun , Chen Lin , Bao Yanqing , Liu Yongping
Published: June 2021

Objective. The aim of this study was to investigate the in vitro antitumor effects of Nidus Vespae on gastric cancer and its ability to promote immune function. Methods. Cell viability was detected by the Cell Counting Kit-8 (CCK-8) assay. Cell cycle distribution and apoptosis were detected using flow cytometry. The THP-1 human monocytic cell line was used as a source of monocytic effector cells for analyzing proliferation and dendritic cell (DC) induction. Enzyme-linked immunosorbent assay was used to detect cytokine production, and multicolor flow cytometry was used to study the phenotype and functionality of THP-1 DCs. Results. A high concentration (>10 mg/mL) of Nidus Vespae decoction (NVD) inhibited SGC-7901 gastric cancer cell growth by inducing G2/M cell cycle arrest and apoptosis. However, a low concentration (≤10 mg/mL) of NVD significantly increased the proliferative ability of THP-1 in serum-containing medium and caused an increase in dendritic protrusions with the typical morphology of DCs compared to the negative control in serum-free medium. The THP-1 DCs had significantly increased expression of cluster of differentiation 11c (CD11c), CD40, CD80, CD83, and CD86, as well as secretion of tumor necrosis factor-alpha. Furthermore, the supernatant of THP-1 DCs significantly inhibited the proliferation of gastric cancer cells by inducing apoptosis and G1/S cell cycle arrest. Conclusions. Our findings suggest that NVD not only directly inhibits the growth of gastric cancer cells but also exerts indirect antitumor effects by enhancing immune function. These results provide an important theoretical basis for the clinical application of Nidus Vespae in gastric cancer treatment.
Lower Somatic Mutation Levels in the λ Light-Chain Repertoires with Chronic HBV Infection
Authors: Hong Binbin , Liu Qiaoling , Li Qiulan , Su Lili , Wang Lizhi
Published: June 2021

To investigate the characteristics of the immunoglobulin light-chain repertoires with chronic HBV infection, the high-throughput sequencing and IMGT/HighV-QUEST were adapted to analyze the κ (IgK) and λ (IgL) light-chain repertoires from the inactive HBV carriers (IHB) and the healthy adults (HH). The comparative analysis revealed high similarity between the κ light-chain repertoires of the HBV carriers and the healthy adults. Nevertheless, the proportion of IGLV genes with ≥90% identity as the germline genes was higher in the IgL light-chain repertoire of the IHB library compared with that of HH library (74.6% vs. 69.1%). Besides, the frequency of amino acid mutations in the CDR1 regions was significantly lower in the IgL light-chain repertoire of the IHB library than that of the HH library (65.52% vs. 56.0%). These results suggested the lower somatic mutation level in the IgL repertoire of IHB library, which might indicate the biased selection of IGLV genes in the IgL repertoire with chronic HBV infection. These findings might lead to a better understanding of the characteristics of the light-chain repertoires of HBV chronically infected individuals.
On a Generalization of Kummer’s Second-Type

F

1

1

and

F

2

2
Authors: Awad Mohamed M.
Published: June 2021

The aim of this paper is to establish a general form of Kummer’s second-type summation theory. By defining a new form for the divided of the Pochhammer symbol

d
+
i

n

/

d

n

, we can develop a general form of Kummer’s second-type summation theorem as

e

−

x
/
2

F

2

2

a
,

i
+
d
;

 

 

 

x

b
+
l
,

d
;

 

in the form of a sum of

e

−

x
/
2

F

1

1

a
;

 

 

 

 

x

b
+
i
;

 

 

for

i
,
l
=
0,1,2
,
…
,

Then, some properties of the generalized Kummer’s second-type summation theorem can yield a number of known and novel results.
Study on the Dynamic Performance of Locally Resonant Plates with Elastic Unit Cell Edges
Authors: Sun Yonggan
Published: June 2021

A Floquet–Bloch approach is employed to demonstrate the stop bands for an infinite locally resonant plate. In addition, the effects of the connection stiffness of the unit cells on the band gap and dynamic performance of a locally resonant plate are analysed. The results show that the degree of inhibition of elastic waves in the band gaps increases rapidly when the connection stiffness of the unit cells increases within the scope of the transition stage stiffness. However, outside of the range of transition stage stiffness, the degree of inhibition of elastic waves in the band gaps basically remains unchanged. This discovery widens the application scope for vibration and noise control using locally resonant plates.
Duchesnea indica Extract Attenuates Coal Fly Ash-Induced Inflammation in Murine Alveolar Macrophages through the NF-Kappa B Pathway
Authors: Ullah H. M. Arif , Lee Yuan Yee , Kim Sung Dae , Rhee Man Hee
Published: June 2021

Duchesnea indica is known as false strawberry, is found in East Asia, and has numerous biological properties. The aim of this study was to investigate the anti-inflammatory effect of Duchesnea indica extract (DIE) on coal fly ash- (CFA-) induced inflammation in murine alveolar macrophages (MH-S). Following the induction of inflammation in MH-S cells by CFA, nitric oxide (NO) was measured to evaluate the anti-inflammatory property of DIE. Cell viability and inflammatory gene expression were analyzed using polymerase chain reaction (PCR). The inflammatory pathway in MH-S cells was determined via western blotting and immunofluorescence (IF) analysis. Finally, the major components of the DIE were identified and separated through ultra-performance liquid chromatography (UPLC) and gas chromatography-mass spectrometry (GC-MS) analysis. Our results showed that the DIE dose-dependently inhibited the CFA-induced NO production in MH-S cells. Moreover, the DIE could suppress the CFA-induced proinflammatory mediators, such as cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). In addition, the inhibitory effect of the DIE on proinflammatory cytokines, including interleukin-6 (IL-6), IL-1β, and tumor necrosis factor-α (TNF-α), was detected with PCR. Moreover, the effect of the DIE on the nuclear factor-κB (NF-κB) pathway in CFA-activated MH-S cells was measured via western blotting. Furthermore, the inhibition of the phosphorylated NF-κB (p-NF-κB) translocation was analyzed using IF assay. The findings of this study indicated that the DIE potentially inhibited the CFA-induced inflammation by blocking the NF-κB inflammatory signaling pathway in MH-S cells and that the DIE might contain favorable anti-inflammatory compounds which may be effective in attenuating lung inflammation.