bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased prevalence of pfdhfr and pfdhps mutations associated with sulfadoxine–pyrimethamine resistance in Plasmodium falciparum isolates from Jazan Region, Southwestern Saudi Arabia: important implications for malaria treatment policy
Authors: Madkhali Aymen M. , Al-Mekhlafi Hesham M. , Atroosh Wahib M. , Ghzwani Ahmad Hassn , Zain Khalid Ammash , Abdulhaq Ahmed A. , Ghailan Khalid Y. , Anwar Alkhansa A. , Eisa Zaki M.
Published: December 2020

Background

Despite significant progress in eliminating malaria from the Kingdom of Saudi Arabia, the disease is still endemic in the southwestern region of the country. Artesunate plus sulfadoxine–pyrimethamine (AS + SP) has been used in Saudi Arabia since 2007 as a first-line treatment for uncomplicated Plasmodium falciparum malaria. This study aimed to investigate the prevalence of mutations associated with resistance to artemisinin and sulfadoxine–pyrimethamine (SP) resistance in P. falciparum parasites circulating in Jazan region, southwestern Saudi Arabia.

Methods

A total of 151 P. falciparum isolates were collected between April 2018 and March 2019 from 12 of the governorates in Jazan region. Genomic DNA was extracted from dried blood spots and amplified using nested PCR. Polymorphisms in the propeller domain of the P. falciparum k13 (pfkelch13) gene and point mutations in the P. falciparum dihydrofolate reductase (pfdhfr) and dihydropteroate synthase (pfdhps) genes were identified by sequencing.

Results

No mutations in the pfkelch13 propeller domain were found in any of the 151 isolates. However, point mutations in the pfdhfr and pfdhps genes were detected in 90.7% (137/151) of the isolates. The pfdhfr double mutations N51I + S108N (i.e. ACICNI haplotype) and triple mutations N51I + C59R + S108N (i.e. ACIRNI haplotype) were detected in 47% and 37.8% of the isolates, respectively. Moreover, the pfdhps single mutation at codon A437G and double mutations A437G + K540E (i.e. SGEAAI haplotype) were observed in 4.6% and 51.7% of the isolates, respectively. Interestingly, 23.8%, 25.1 and 12.6% of the isolates had quintuple, quadruple and triple mutated combined pfdhfr–pfdhps genotypes, respectively. Furthermore, significant associations were found between the prevalence of mutant haplotypes and the age, gender and nationality of the patients (P < 0.05).

Conclusion

This study revealed a high prevalence of point mutations in the pfdhfr and pfdhps genes of P. falciparum isolates from Jazan region, with quintuple and quadruple mutant pfdhfr–pfdhps genotypes reported for the first time in Saudi Arabia and the Arabian Peninsula. Despite the absence of the pfkelch13 mutation in the isolates examined, the pfdhfr and pfdhps mutations undermine the efficacy of SP partner drug, thereby threatening the main falciparum malaria treatment policy in Saudi Arabia, i.e. the use of AS + SP. Therefore, the continuous molecular and in-vivo monitoring of ACT efficacy in Jazan region is highly recommended.
Association between commensality with depression and suicidal ideation of Korean adults: the sixth and seventh Korean National Health and Nutrition Examination Survey, 2013, 2015, 2017
Authors: Son Yoon Hee , Oh Sarah Soyeon , Jang Sung-In , Park Eun-Cheol , Park So-Hee
Published: December 2020

Objectives

This study investigated whether commensality (eating a meal with others) is associated with mental health (depression, suicidal ideation) in Korean adults over 19 years old.

Methods

Our study employed data from the sixth and seventh Korea National Health and Nutritional Examination Surveys (KNHANES) for 2013, 2015, and 2017. The study population consisted of 14,125 Korean adults (5854 men and 8271 women). In this cross-sectional study, data were analyzed with the Rao-Scott chi-square test and multiple logistic regression to evaluate the association between commensality(0[includes skipping meals] to 3 times eating meals together) and both depression and suicidal ideation using select questions from the Mental Health Survey. By setting socioeconomic factors, health conditions, and behavioral factors as confounders, we conducted a subgroup analysis to reveal the effect on depression and suicidal ideation commensality.

Results

Commensality was significantly associated with depression and suicidal ideation (p < 0.05). In both sexes, people who ate fewer meals together had poorer mental health. In a subgroup analysis, we revealed greater odds of developing depression in men when living in rural areas and belonging to low-income groups. In contrast, greater odds of suicidal ideation in men who ate alone when living in the city and belonging to high-income groups. On the other hand, Women in every region had greater odds of being depressed if they ate alone. And greater odds of suicidal ideation in women who ate alone when living in the city and belonging to medium-high income groups.

Conclusions

Our analysis confirmed that Korean adults with lower chance of commensality had greater risk of developing depression and suicidal ideation. And it could be affected by individuals’ various backgrounds including socioeconomic status. As a result, to help people with depression and prevent a suicidal attempt, this study will be baseline research for social workers, educators and also policy developers to be aware of the importance of eating together.
Dexamethasone and lidocaine suppress eosinophilopoiesis from umbilical cord blood cells
Authors: Muraki Masato , Kita Hirohito , Gleich Gerald J.
Published: December 2020

Background

Eosinophils play an important role in allergic inflammation. Glucocorticosteroids have been used as an anti-inflammatory medication for inflammatory diseases involving eosinophil infiltration. Some effect of nebulized lidocaine has been reported when treating certain patients with asthma, which is also an inflammatory disease. The goal of this study was to examine the effects of dexamethasone and lidocaine on eosinophil proliferation and differentiation using a model of human umbilical cord blood mononuclear cells (UCMC) cultured with IL-5.

Methods

UCMC were cultured with IL-5 (5 ng/mL) for 4 weeks. The effects of dexamethasone and lidocaine on the number and morphology of eosinophilic cells were visualized with Wright-Giemsa and cyanide-resistant peroxidase stains. Moreover, the effect on eosinophil-derived neurotoxin (EDN) and eosinophil peroxidase (EPX) contents in cultured cells were evaluated using radioimmunoassay.

Results

The number of eosinophilic cells and EDN and EPX content in cultured cells increased in a time-dependent manner in the presence of IL-5. Dexamethasone treatment slightly decreased the number of eosinophilic cells in one week, but this effect was lost in 2–4 weeks. Macrophages in cultured UCMC treated with dexamethasone contained more eosinophil granule proteins. Both EDN and EPX content in cultured cells were reduced by dexamethasone. Lidocaine decreased the number of eosinophilic cells and reduced both EDN and EPX contents in cultured cells.

Conclusions

Dexamethasone suppressed the production of eosinophil granule proteins and may also induce apoptosis of eosinophils, while lidocaine suppresses eosinophilopoiesis.
Predictors of skin and soft tissue infections among sample of rural residents who inject drugs
Authors: Baltes Amelia , Akhtar Wajiha , Birstler Jen , Olson-Streed Heidi , Eagen Kellene , Seal David , Westergaard Ryan , Brown Randall
Published: December 2020

Introduction

Skin and soft tissue infections (SSTIs) are among the leading causes of morbidity and mortality for people who inject drugs (PWID). Studies demonstrate that certain injection practices correlate with SSTI incidence among PWID. The opioid epidemic in the USA has particularly affected rural communities, where access to prevention and treatment presents unique challenges. This study aims to estimate unsafe injection practices among rural-dwelling PWID; assess treatments utilized for injection related SSTIs; and gather data to help reduce the overall risk of injection-related SSTIs.

Methods

Thirteen questions specific to SSTIs and injection practices were added to a larger study assessing unmet health care needs among PWID and were administered at six syringe exchange programs in rural Wisconsin between May and July 2019. SSTI history prevalence was estimated based on infections reported within one-year prior of response and was compared to self-reported demographics and injection practices.

Results

Eighty responses were collected and analyzed. Respondents were white (77.5%), males (60%), between the ages 30 and 39 (42.5%), and have a high school diploma or GED (38.75%). The majority of respondents (77.5%) reported no history of SSTI within the year prior to survey response. Females were over three times more likely to report SSTI history (OR = 3.07, p = 0.038) compared to males. Water sources for drug dilution (p = 0.093) and frequency of injecting on first attempt (p = 0.037), but not proper skin cleaning method (p = 0.378), were significantly associated with a history of SSTI. Injecting into skin (p = 0.038) or muscle (p = 0.001) was significantly associated with a history of SSTI. Injection into veins was not significantly associated with SSTI (p = 0.333).

Conclusion

Higher-risk injection practices were common among participants reporting a history of SSTIs in this rural sample. Studies exploring socio-demographic factors influencing risky injection practices and general barriers to safer injection practices to prevent SSTIs are warranted. Dissemination of education materials targeting SSTI prevention and intervention among PWID not in treatment is warranted.
Interplay between endoplasmic reticulum stress and non-coding RNAs in cancer
Authors: Zhao Tianming , Du Juan , Zeng Hui
Published: December 2020

To survive, cancer cells are subjected to various internal and external adverse factors, including genetic mutations, hypoxia, nutritional deficiencies, and drug toxicity. All of these factors result in the accumulation of unfolded proteins in the endoplasmic reticulum, which leads to a condition termed endoplasmic reticulum stress (ER stress) and triggers the unfolded protein response (UPR). UPR downstream components strictly control transcription and translation reprogramming to ensure selective gene expression, including that of non-coding RNA (ncRNAs), to adapt to adverse environments. NcRNAs, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), play important roles in regulating target gene expression and protein translation, and their aberrant expression is related to tumor development. Dysregulation of ncRNAs is involved in the regulation of various cellular characteristics of cancer cells, including growth, apoptosis, metastasis, angiogenesis, drug sensitivity, and tumor stem cell properties. Notably, ncRNAs and ER stress can regulate each other and collaborate to determine the fate of tumor cells. Therefore, investigating the interaction between ER stress and ncRNAs is crucial for developing effective cancer treatment and prevention strategies. In this review, we summarize the ER stress-triggered UPR signaling pathways involved in carcinogenesis followed by the mutual regulation of ER stress and ncRNAs in cancer, which provide further insights into the understanding of tumorigenesis and therapeutic strategies.
Impact of advance directives on the variability between intensivists in the decisions to forgo life-sustaining treatment
Authors: Smirdec Margot , Jourdain Mercé , Guastella Virginie , Lambert Céline , Richard Jean-Christophe , Argaud Laurent , Jaber Samir , Klouche Kada , Medard Anne , Reignier Jean , Rigaud Jean-Philippe , Doise Jean-Marc , Chabanne Russell , Souweine Bertrand , Bourenne Jeremy , Delmas Julie , Bertrand Pierre-Marie , Verdier Philippe , Quenot Jean-Pierre , Aubron Cecile , Eisenmann Nathanael , Asfar Pierre , Fratani Alexandre , Dellamonica Jean , Terzi Nicolas , Constantin Jean-Michel , Van Lander Axelle , Guerin Renaud , Pereira Bruno , Lautrette Alexandre
Published: December 2020

Background

There is wide variability between intensivists in the decisions to forgo life-sustaining treatment (DFLST). Advance directives (ADs) allow patients to communicate their end-of-life wishes to physicians. We assessed whether ADs reduced variability in DFLSTs between intensivists.

Methods

We conducted a multicenter, prospective, simulation study. Eight patients expressed their wishes in ADs after being informed about DFLSTs by an intensivist-investigator. The participating intensivists answered ten questions about the DFLSTs of each patient in two scenarios, referring to patients’ characteristics without ADs (round 1) and then with (round 2). DFLST score ranged from 0 (no-DFLST) to 10 (DFLST for all questions). The main outcome was variability in DFLSTs between intensivists, expressed as relative standard deviation (RSD).

Results

A total of 19,680 decisions made by 123 intensivists from 27 ICUs were analyzed. The DFLST score was higher with ADs than without (6.02 95% CI [5.85; 6.19] vs 4.92 95% CI [4.75; 5.10], p < 0.001). High inter-intensivist variability did not change with ADs (RSD: 0.56 (round 1) vs 0.46 (round 2), p = 0.84). Inter-intensivist agreement on DFLSTs was weak with ADs (intra-class correlation coefficient: 0.28). No factor associated with DFLSTs was identified. A qualitative analysis of ADs showed focus on end-of-life wills, unwanted things and fear of pain.

Conclusions

ADs increased the DFLST rate but did not reduce variability between the intensivists. In the decision-making process using ADs, the intensivist’s decision took priority. Further research is needed to improve the matching of the physicians’ decision with the patient’s wishes.

Trial registration ClinicalTrials.gov Identifier: NCT03013530. Registered 6 January 2017; https://clinicaltrials.gov/ct2/show/NCT03013530.
Mutant p53 drives the loss of heterozygosity by the upregulation of Nek2 in breast cancer cells
Authors: Ghaleb Amr , Padellan Malik , Marchenko Natalia
Published: December 2020

Background

Mutations in one allele of the TP53 gene in early stages are frequently followed by the loss of the remaining wild-type p53 (wtp53) allele (p53LOH) during tumor progression. Despite the strong notion of p53LOH as a critical step in tumor progression, its oncogenic outcomes that facilitate the selective pressure for p53LOH occurrence were not elucidated.

Methods

Using MMTV;ErbB2 mouse model of breast cancer carrying heterozygous R172H p53 mutation, we identified a novel gain-of-function (GOF) activity of mutant p53 (mutp53): the exacerbated loss of wtp53 allele in response to γ-irradiation.

Results

As consequences of p53LOH in mutp53 heterozygous cells, we observed profound stabilization of mutp53 protein, the loss of p21 expression, the abrogation of G2/M checkpoint, chromosomal instability, centrosome amplification, and transcriptional upregulation of mitotic kinase Nek2 (a member of Never in Mitosis (NIMA) Kinases family) involved in the regulation of centrosome function. To avoid the mitotic catastrophe in the absence of G2/M checkpoint, cells with centrosome amplification adapt Nek2-mediated centrosomes clustering as pro-survival mutp53 GOF mechanism enabling unrestricted proliferation and clonal expansion of cells with p53LOH. Thus, the clonal dominance of mutp53 cells with p53LOH may represent the mechanism of irradiation-induced p53LOH. We show that pharmacological and genetic ablation of Nek2 decreases centrosome clustering and viability of specifically mutp53 cells with p53LOH.

Conclusion

In a heterogeneous tumor population, Nek2 inhibition may alter the selective pressure for p53LOH by contraction of the mutp53 population with p53LOH, thus, preventing the outgrowth of genetically unstable, more aggressive cells.
Computation offloading to edge cloud and dynamically resource-sharing collaborators in Internet of Things
Authors: Mu Siqi , Zhong Zhangdui
Published: December 2020

With the diversity of the communication technology and the heterogeneity of the computation resources at network edge, both the edge cloud and peer devices (collaborators) can be scavenged to provide computation resources for the resource-limited Internet-of-Things (IoT) devices. In this paper, a novel cooperative computing paradigm is proposed, in which the computation resources of IoT device, opportunistically idle collaborators and dedicated edge cloud are fully exploited. Computation/offloading assistance is provided by collaborators at idle/busy states, respectively. Considering the channel randomness and opportunistic computation resource share of collaborators, we study the stochastic offloading control for an IoT device, regarding how much computation load is processed locally, offloaded to the edge cloud and a collaborator. The problem is formulated into a finite horizon Markov decision problem with the objective of minimizing the expected total energy consumption of the IoT device and the collaborator, subject to satisfying the hard computation deadline constraint. Optimal offloading policy is derived based on the stochastic optimization theory, which demonstrates that the energy consumption can be reduced by a proportional factor through the cooperative computing. More energy saving is achieved with better wireless channel condition or higher computation energy efficiency of collaborators. Simulation results validate the optimality of the proposed policy and the efficiency of the cooperative computing between end devices and edge cloud, compared to several other offloading schemes.
Empirical and finite element based stability analysis of highway cut slopes in Uttarakhand Himalayan terrain, India
Authors: Singh Hari Om , Ansari Tariq Anwar , Singh T. N. , Singh K. H.
Published: December 2020

The present paper deals with different empirical methods and finite element method of slope stability analysis along National Highway (NH)-7, in Uttarakhand, India. The highway is only path in the hilly terrain of Lesser Himalayan for the public transport and have strategic importance due to militaries possession routes. This route is also significant due to having many holistic places, connecting to this. There was numerous landslides happened along the Highway in past due to various natural and anthropogenic activities. Hence, keeping an eye to the socio-economic development of the distant area, slope stability analysis is very crucial along the road cut sections. To identify the vulnerable locations and to collect the geotechnical data, the field investigation was carried out between Shivpuri to Byasi along NH-7 in Garhwal, Uttarakhand. Then geotechnical data was intended followed by rock mass characteristic, kinematic analysis and Qslope stability. Additionally, to review the stability results, numerical simulation (finite element method) was employed and slope mass behavior and failure mechanism of cut slopes were also evaluated. The rock mass characteristic and kinematic analysis illustrate normal and good variety of rock mass mainly wedge mode with flexural toppling of failure. The slope mass rating, continuous slope mass rating and also Qslope stability analysis showed, road cut slopes are critically stable and unstable. The results of different empirical methods shows a decent correlation between them. Further the numerical simulation analysis also evaluates that two cut slopes are unstable and other one is critically stable. This substantial empirical and numerical analysis of cut slopes provides a collective approach to stable and develop the holistic road corridor in Himalayan terrain.
Ultrasound-guided inferior alveolar nerve block for trismus during dental treatment: a case report
Authors: Kojima Yuki , Sendo Ryozo , Ohno Sachi , Sugimura Mitsutaka
Published: December 2020

Background

Temporomandibular disorder (TMD) is a broad term that encompasses pain and/or dysfunction of the masticatory musculature and TM joints (TMJs). When TMD becomes a chronic condition, the symptoms are extremely difficult to manage and require multiple interventions.

Case presentation

A woman in her 50s developed TMD after a traffic accident 30 years ago. The patient presented with severe trismus due to TMJ pain and a maximum mouth opening of 20 mm. Ultrasound-guided inferior alveolar nerve block (IANB) was performed with ropivacaine. After IANB, the pain during mouth opening subsided and the maximum mouth opening improved to 40 mm. Dental treatment could be performed without difficulty and the patient could keep her mouth open throughout the treatment.

Conclusions

Treatments for chronic TMD are limited and it is necessary to identify the precise etiology before choosing a treatment option. In this patient, ultrasound-guided IANB proved to be effective in relieving TMD-related trismus.
A literature review on the parvovirus B19 infection in sickle cell anemia and β-thalassemia patients
Authors: Soltani Saber , Zakeri Armin , Tabibzadeh Alireza , Zandi Milad , Ershadi Elham , Akhavan Rezayat Sara , Khaseb Sanaz , Zakeri Amir mohammad , Ashtar Nakhaei Mohammadvala , Afzali Shervin , Farahani Abbas
Published: December 2020

Background

Parvovirus B19 is the causative agent for erythema infectiosum, and also as a potentially life-threatening infectious agent, it is mainly presented in high erythrocyte turnover patients. Sickle cell disease (SCD) is an inherited monogenic hematological disorder resulting from the mutations in the hemoglobin β-chain gene. Thalassemia is a hereditary hematological syndrome that happens in consequence of deficiencies in the production of one or more globin chains. We summarize current knowledge about the prevalence rates of the parvovirus B19 infection in sickle cell anemia and thalassemia patients.

Methods

Several online databases were searched including, Scopus, EMBASE, Web of Science, Google Scholar, and PubMed, which were performed amidst 2009–2019 by using distinct keywords: “Thalassemia,” “Parvovirus,” “Anemia,” “Sickle cell anemia,” “parvoviridae,” “parvoviridae infection,” and “parvovirus B19.”

Results

Search results indicated 4 and 7 studies for the prevalence of the parvovirus B19 in β-thalassemia and SCD, respectively. Among the β-thalassemia patients, the B19V seroprevalence for IgG and IgM were ranged from 18.2–81% and 14.5–41.1%, respectively; meanwhile, B19V DNA positively results was 4–15.3%. Moreover, in the SCD group, the extent of B19V IgG was varied from 37.6 to 65.9% and that of IgM was in a range of 2.9–30%, and the DNA detection rate was 4–54%.

Conclusion

B19V seroprevalence changes in several conditions including, different epidemiological features, socio-economic status, and overpopulation. Age can expand the incidence of anti-B19V IgG/IgM in SCD and beta-thalassemia patients. Reinfection and diverse genotypes are relevant factors in the seroprevalence of B19v. The patients’ immunological-hematological station and higher abundance of transfusions can affect the B19V seroprevalence in SCD and beta-thalassemia group. Further investigations in this field could be suggested to better understand the virus distribution in this susceptible population of patients.
Role of diffusion-weighted magnetic resonance imaging in assessment of mammographically detected asymmetric densities
Authors: Zidan Mohamed , Saad Shimaa Ali , Abo Elhamd Eman , Galal Hosam Eldin , Elkady Reem
Published: December 2020

Background

Asymmetric breast density is a potentially perplexing finding; it may be due to normal hormonal variation of the parenchymal pattern and summation artifact or it may indicate an underlying true pathology. The current study aimed to identify the role of diffusion-weighted imaging (DWI) and the apparent diffusion coefficient (ADC) values in the assessment of breast asymmetries.

Results

Fifty breast lesions were detected corresponding to the mammographic asymmetry. There were 35 (70%) benign lesions and 15 (30%) malignant lesions. The mean ADC value was 1.59 ± 0.4 × 10–3 mm2/s for benign lesions and 0.82 ± 0.3 × 10–3 mm2/s for malignant lesions. The ADC cutoff value to differentiate between benign and malignant lesions was 1.10 × 10–3 mm2/s with sensitivity 80%, specificity 88.6%, positive predictive value 75%, negative predictive value 91%, and accuracy 86%. Best results were achieved by implementation of the combined DCE-MRI and DWI protocol, with sensitivity 93.3%, specificity 94.3%, positive predictive value 87.5%, negative predictive value 97.1%, and accuracy 94%.

Conclusion

Dynamic contrast-enhanced MRI (DCE-MRI) was the most sensitive method for the detection of the underlying malignant pathology of breast asymmetries. However, it provided a limited specificity that may cause improper final BIRADS classification and may increase the unnecessary invasive procedures. DWI was used as an adjunctive method to DCE-MRI that maintained high sensitivity and increased specificity and the overall diagnostic accuracy of breast MRI examination. Best results can be achieved by the combined protocol of DCE-MRI and DWI.
Cross hole sonic test results for analysis of pile load test
Authors: Bagui Swapan Kunar , Puri S. K. , Subbiah K.
Published: December 2020

Quality of concrete for pile can be checked using Cross-hole Sonic Logging (CSL) Test. A processing method wide-band CSL data is presented herein. First Time Arrival (FTA) is an important consideration. In pile capacity analysis or CSL analysis, it is assumed that pile cross section is uniform with uniform value of elastic modulus of concrete but in real practice both are non-uniform. The procedure identifies the location accuracy and further characterizes the features of the defect. FTA is used to find out the location of the distress in the pile. This method identifies the exact location of any void or defect inside the rebar cage of a drilled shaft. This method provides a significant improvement to current techniques used in quality control during construction of bridges. In this present paper, the analysis has been carried out based on uniform and non-uniform values of pile cross section and E value of concrete. Cross hole sonic and pile load test using O-Cell were carried out on same pile at 7 and 28 days of concreting. Same pipes were used for base grout after cross hole sonic test. These results were used to analyze O-cell test results based on a case study and presented in this paper. The distribution of skin frication and skin friction force has also been presented herein with both uniform and non-uniform cross section and E values of concrete. Based on the field test results and analysis a simplified methodology, has been proposed in this paper, for development of Equivalent Top Down Loading with consideration of elastic shortening of pile and surrounding soil for both cases i.e., uniform and non-uniform E values and pile cross sections.
Multiorgan Point-of-Care Ultrasound in a Patient With Coronavirus Disease 2019 Pneumonia Complicated by Subarachnoid Hemorrhage and Pulmonary Embolism
Authors: Haider Alaa , Schmitt Christoph , Greim Clemens-Alexander
Published: December 2020

Morbidity and mortality associated with the pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (coronavirus disease 2019 [COVID-19]) are not only due to acute respiratory distress syndrome but also related to multiorgan involvement and dysfunction. In this report, we present a critically ill patient with severe COVID-19 pneumonia, during which he required extracorporeal membrane oxygenation and suffered from multiple complications. Bedside sonography became an important tool to manage the patient by adapting artificial ventilation parameters and played a key role in the diagnosis of thrombotic events and the monitoring of subarachnoid hemorrhage that unexpectedly complicated the case.
PHOSPHORYLETHANOLAMINE CYTIDYLYLTRANSFERASE 1 modulates flowering in a florigen-independent manner by regulating SVP
Authors: Susila Hendry , Nasim Zeeshan , Gawarecka Katarzyna , Jung Ji-Yul , Jin Suhyun , Youn Geummin , Ahn Ji Hoon
Published: December 2020

PHOSPHORYLETHANOLAMINE CYTIDYLYLTRANSFERASE 1 (PECT1) regulates phosphatidylethanolamine biosynthesis and controls the phosphatidylethanolamine: phosphatidylcholine ratio in Arabidopsis thaliana. Previous studies suggested that PECT1 regulates flowering time by modulating the interaction between phosphatidylcholine and FLOWERING LOCUS T (FT), a florigen, in the shoot apical meristem (SAM). Here, we show that knock-down of PECT1 by artificial microRNA in the SAM (pFD::amiR-PECT1) accelerated flowering under inductive and even non-inductive conditions, where FT transcription is almost absent, and in ft-10 twin sister of ft-1 double mutants under both conditions. Transcriptome analyses suggested that PECT1 affects flowering by regulating SHORT VEGETATIVE PHASE (SVP) and GIBBERELLIN 20 OXIDASE 2 (GA20ox2). SVP mis-expression in the SAM suppressed the early flowering of pFD::amiR-PECT1 plants. pFD::amiR-PECT1 plants showed increased gibberellin (GA) levels in the SAM, concomitant with the reduction of REPRESSOR OF GA1-3 levels. Consistent with this, GA treatment had little effect on flowering time of pFD::amiR-PECT1 plants and the GA antagonist paclobutrazol strongly affected flowering in these plants. Together, these results suggest that PECT1 also regulates flowering time through a florigen-independent pathway, modulating SVP expression and thus regulating GA production.
EPySeg: a coding-free solution for automated segmentation of epithelia using deep learning
Authors: Aigouy Benoit , Cortes Claudio , Liu Shanda , Prud'Homme Benjamin
Published: December 2020

Epithelia are dynamic tissues that self-remodel during their development. During morphogenesis, the tissue-scale organization of epithelia is obtained through a sum of individual contributions of the cells constituting the tissue. Therefore, understanding any morphogenetic event first requires a thorough segmentation of its constituent cells. This task, however, usually implies extensive manual correction, even with semi-automated tools. Here we present EPySeg, an open-source, coding-free software that uses deep learning to segment membrane-stained epithelial tissues automatically and very efficiently. EPySeg, which comes with a straightforward graphical user interface, can be used as a python package on a local computer, or on the cloud via Google Colab for users not equipped with deep-learning compatible hardware. By substantially reducing human input in image segmentation, EPySeg accelerates and improves the characterization of epithelial tissues for all developmental biologists.
Retromer retrieves the Wilson disease protein ATP7B from endolysosomes in a copper-dependent manner
Authors: Das Santanu , Maji Saptarshi , Ruturaj  , Bhattacharya Indira , Saha Tanusree , Naskar Nabanita , Gupta Arnab
Published: December 2020

The Wilson disease protein, ATP7B maintains copper (herein referring to the Cu+ ion) homeostasis in the liver. ATP7B traffics from trans-Golgi network to endolysosomes to export excess copper. Regulation of ATP7B trafficking to and from endolysosomes is not well understood. We investigated the fate of ATP7B after copper export. At high copper levels, ATP7B traffics primarily to acidic, active hydrolase (cathepsin-B)-positive endolysosomes and, upon subsequent copper chelation, returns to the trans-Golgi network (TGN). At high copper, ATP7B colocalizes with endolysosomal markers and with a core member of retromer complex, VPS35. Knocking down VPS35 did not abrogate the copper export function of ATP7B or its copper-responsive anterograde trafficking to vesicles; rather upon subsequent copper chelation, ATP7B failed to relocalize to the TGN, which was rescued by overexpressing wild-type VPS35. Overexpressing mutants of the retromer complex-associated proteins Rab7A and COMMD1 yielded a similar non-recycling phenotype of ATP7B. At high copper, VPS35 and ATP7B are juxtaposed on the same endolysosome and form a large complex that is stabilized by in vivo photoamino acid labeling and UV-crosslinking. We demonstrate that retromer regulates endolysosome to TGN trafficking of copper transporter ATP7B in a manner that is dependent upon intracellular copper.
Similar foraging energetics of two sympatric albatrosses despite contrasting life histories and wind-mediated foraging strategies
Authors: Kroeger Caitlin E. , Crocker Daniel E. , Orben Rachael A. , Thompson David R. , Torres Leigh G. , Sagar Paul M. , Sztukowski Lisa A. , Andriese Timothy , Costa Daniel P. , Shaffer Scott A.
Published: December 2020

Understanding the environmental and behavioral factors that influence how organisms maintain energy balance can inform us about their potential resiliency to rapid environmental changes. Flexibility in maintaining energy balance is particularly important to long-lived, central-place foraging seabirds that are constrained when locating food for offspring in a dynamic ocean environment. To understand the role of environmental interactions, behavioral flexibility and morphological constraints on energy balance, we used doubly labeled water to measure the at-sea daily energy expenditure (DEE) of two sympatrically breeding seabirds, Campbell (Thalassarche impavida) and grey-headed (Thalassarche chrysostoma) albatrosses. We found that species and sexes had similar foraging costs, but DEE varied between years for both species and sexes during early chick rearing in two consecutive seasons. For both species, greater DEE was positively associated with larger proportional mass gain, lower mean wind speeds during water take-offs, greater proportions of strong tailwinds (>12 m s−1), and younger chick age. Greater proportional mass gains were marginally more costly in male albatrosses that already have higher wing loading. DEE was higher during flights with a greater proportion of strong headwinds for grey-headed albatrosses only. Poleward winds are forecasted to intensify over the next century, which may increase DEE for grey-headed albatrosses that heavily use this region during early chick rearing. Female Campbell albatrosses may be negatively affected by forecasted slackening winds at lower latitudes due to an expected greater reliance on less energy efficient sit-and-wait foraging strategies. Behavioral plasticity associated with environmental variation may influence future population responses to climate change of both species.
Life-long exposure to hypoxia affects metabolism and respiratory physiology across life stages in high-altitude deer mice (Peromyscus maniculatus)
Authors: Ivy Catherine M. , Scott Graham R.
Published: December 2020

Hypoxia exposure can have distinct physiological effects between early developmental and adult life stages, but it is unclear how the effects of hypoxia may progress during continuous exposure throughout life. We examined this issue in deer mice (Peromyscus maniculatus) from a population native to high altitude. Mice were bred in captivity in each of three treatment groups: normoxia (controls); life-long hypoxia (∼12 kPa O2 from conception to adulthood); and parental hypoxia (normoxia from conception to adulthood, but parents previously exposed to hypoxia). Metabolic, thermoregulatory, and ventilatory responses to progressive stepwise hypoxia and haematology were then measured at post-natal day (P) 14 and 30 and/or in adulthood. Life-long hypoxia had consistent effects across ages on metabolism, attenuating the declines in O2 consumption rate (VO2) and body temperature during progressive hypoxia compared to control mice. However, life-long hypoxia had age-specific effects on breathing, blunting the hypoxia-induced increases in air convection requirement (quotient of total ventilation and VO2) at P14 and P30 only, but then shifting breathing pattern towards deeper and/or less frequent breaths at P30 and adulthood. Hypoxia exposure also increased blood-O2 affinity at P14 and P30, in association with an increase in arterial O2 saturation in hypoxia at P30. In contrast, parental hypoxia had no effects on metabolism or breathing, but it increased blood-O2 affinity and decreased red cell hemoglobin content at P14 (but not P30). Therefore, hypoxia exposure has some consistent effects across early life and adulthood, and some other effects that are unique to specific life stages.
Three auditory brainstem response (ABR) methods tested and compared in two anuran species
Authors: Lauridsen Tanya B. , Brandt Christian , Christensen-Dalsgaard Jakob
Published: December 2020

Hearing sensitivity has been extensively investigated, often by measuring the auditory brainstem response (ABR). ABR measurements are relatively non-invasive, easy to reproduce, and allow the assessment of sensitivity when psychophysical data are difficult to obtain. However, the experimental methods differ greatly in respect to stimulation, which may result in different audiograms.

We used three different methods in the same individual frogs: Stimulating with brief tone bursts (tABR), long-duration tones (ltABR), and masked ABR (mABR) where transients are masked by a long-duration sinusoid, and the sensitivity is assessed by the difference between unmasked and masked ABR.

We measured sensitivity in a range from 100 to 3500 Hz, and the resulting audiograms show two sensitivity peaks at 400-600 Hz and 1500-1600 Hz (both sensitive down to 30 dB re. 20 µPa). We found similar results below 1000 Hz, but when stimulating with long-duration tones, the sensitivity decreased more rapidly above this frequency. We showed that the frequency specificity of tone bursts becomes poorly defined with shorter duration at low frequencies. Comparisons between subjectively (visual inspection by researchers) and objectively (thresholds defined by SNR) defined audiograms showed very little variation. In conclusion the mABR method gave the most sensitive audiograms. The tABR method showed a similar audiogram, when using relatively long-duration tone bursts (25 ms). The ltABR method is not a good choice for studying hearing thresholds above 1000 Hz, because of the bias introduced by spike rate saturation in the nerve fibers and their inability to phase lock.
Low incubation temperature retards the development of cold tolerance in a precocial bird
Authors: Nord Andreas , Nilsson Jan-Åke
Published: December 2020

Incubating birds trade off self-maintenance for keeping eggs warm. This causes lower incubation temperature in more challenging conditions, with consequences for a range of offspring traits. It is not yet clear how low developmental temperature affects cold tolerance early in life. This is ecologically important because before full thermoregulatory capacity is attained, precocial chicks must switch between foraging and being brooded when their body temperature declines. Hence, we studied how cold tolerance during conditions similar to a feeding bout in the wild was affected by incubation temperature in Japanese quail (Coturnix japonica). Cold-incubated (35.5°C) chicks took the longest to develop, hatched smaller, and remained smaller during their first week of life compared to chicks incubated at higher temperatures (37.0°C, 38.5°C). This was reflected in increased cooling rate and reduced homeothermy, probably on account of reductions in both heat-producing capacity and insulation. Lower cold tolerance could exacerbate other temperature-linked phenotypic effects and, hence, also the trade-off between future and current reproduction from the perspective of the incubating parent.
Chyle Leak Following Radical En Bloc Esophagectomy with Two-Field Nodal Dissection: Predisposing Factors, Management, and Outcomes
Authors: Milito Pamela , Chmelo Jakub , Dunn Lorna , Kamarajah Sivesh K. , Madhavan Anantha , Wahed Shajahan , Immanuel Arul , Griffin S. Michael , Phillips Alexander W.
Published: December 2020

Background

Chyle leak is an uncommon complication following esophagectomy, accounting for significant morbidity and mortality; however, the optimal treatment for the chylothorax is still controversial.

Objective

The aim of this study was to evaluate the incidence, management, and outcomes of chyle leaks within a specialist esophagogastric cancer center.

Methods

Consecutive patients undergoing esophagectomy for esophageal cancers (adenocarcinoma or squamous cell carcinoma) between 1997 and 2017 at the Northern Oesophagogastric Unit were included from a contemporaneously maintained database. Primary outcome was overall survival, while secondary outcomes were overall complications, anastomotic leaks, and pulmonary complications.

Results

During the study period, 992 patients underwent esophagectomy for esophageal cancers, and 5% (n = 50) of them developed chyle leaks. There was no significant difference in survival in patients who developed a chyle leak compared with those who did not (median: 40 vs. 45 months; p = 0.60). Patients developing chyle leaks had a significantly longer length of stay in critical care (median: 4 vs. 2 days; p = 0.002), but no difference in total length of hospital stay.

Conclusion

Chyle leak remains a complication following esophagectomy, with limited understanding on its pathophysiology in postoperative recovery. However, these data indicate chyle leak does not have a long-term impact on patients and does not affect long-term survival.
The viral protein NSP1 acts as a ribosome gatekeeper for shutting down host translation and fostering SARS-CoV-2 translation
Authors: Tidu Antonin , Janvier Aurélie , Schaeffer Laure , Sosnowski Piotr , Kuhn Lauriane , Hammann Philippe , Westhof Eric , Eriani Gilbert , Martin Franck
Published: December 2020

SARS-CoV-2 coronavirus is responsible for the Covid-19 pandemic. In the early phase of infection, the single-strand positive RNA genome is translated into nonstructural proteins (NSP). One of the first proteins produced during viral infection, NSP1, binds to the host ribosome and blocks the mRNA entry channel. This triggers translation inhibition of cellular translation. Despite the presence of NSP1 on the ribosome, viral translation proceeds, however. The molecular mechanism of the so-called viral evasion to NSP1 inhibition remains elusive. Here, we confirm that viral translation is maintained in the presence of NSP1 and we show that the evasion to NSP1-inhibition is mediated by the cis-acting RNA hairpin SL1 in the 5′UTR of SARS-CoV-2. Only the apical part of SL1 is required for viral translation. We further show that NSP1 remains bound on the ribosome during viral translation. We suggest that the interaction between NSP1 and SL1 frees the mRNA accommodation channel while maintaining NSP1 bound to the ribosome. Thus, NSP1 acts as a ribosome gatekeeper, shutting down host translation and fostering SARS-CoV-2 translation in the presence of the SL1 5′UTR hairpin. SL1 is also present and necessary for translation of subgenomic RNAs in the late phase of the infectious program. Consequently, therapeutic strategies targeting SL1 should affect viral translation at early and late stages of infection. Therefore, SL1 might be seen as a genuine “Achilles heel” of the virus.
Viral Economies
Authors: Kyriakopoulos Leandros
Published: December 2020

The article examines the Covid-19 pandemic by investigating the ways in which viruses are mapped out through the biosciences and recognized as threats in informational systems. Two examples are analyzed that, although seemingly unrelated, intersect the assemblages of biological and communicational networks. The first one concerns the speed at which a third of the world's population was quarantined. The second one involves the readiness of the material-technical infrastructure to support, and the political planning to transfer, a multitude of social and labour activities onto digital platforms. The adjective ‘viral’ highlights the metonymic ways in which digital media locate the different economies of gene formation, circulation and communication of subjects, transport of goods and political decision-making, and adapt them in favour of the technologic of the network. And what is suggested is to view the advent of Covid-19 within the cultural logic of new media in order to understand the horizon of an oncoming modernity.
Perspectives on public health interventions in the management of the COVID-19 pandemic in Thailand
Authors: Pan-ngum Wirichada , Poomchaichote Tassawan , Peerawaranun Pimnara , Kulpijit Natinee , Osterrieder Anne , Waithira Naomi , Mukaka Mavuto , Naemiratch Bhensri , Chanviriyavuth Rita , Asarath Supa-at , Ruangkajorn Supanat , Kannika Noppadon , Cheah Phaik Yeong
Published: December 2020

Background: Any government needs to react quickly to a pandemic and make decisions on healthcare interventions locally and internationally with little information regarding the perceptions of people and the reactions they may receive during the implementation of restrictions.

Methods: We report an anonymous online survey in Thailand conducted in May 2020 to assess public perceptions of three interventions in the Thai context: isolation, quarantine and social distancing. A total of 1,020 participants, of whom 52% were women, responded to the survey.

Results: Loss of income was the main concern among respondents (>80% for all provinces in Thailand). Traditional media and social media were important channels for communication during the pandemic. A total of 92% of respondents reported that they changed their social behaviour even before the implementation of government policy with 94% reporting they performed social distancing, 97% reported using personal protective equipment such as masks and 95% reported using sanitizer products.

Conclusions: This study showed a high level of compliance from individuals with government enforced or voluntarily controls such as quarantine, isolation and social distancing in Thailand. The findings from this study can be used to inform future government measures to control the pandemic and to shape communication strategies.
Wstęp
Authors: Świątek Adam
Published: December 2020

Kresy to pojęcie, które – przynajmniej zwyczajowo – przyjęło się rozumieć jako teren dawnych polskich aspiracji, kulturowego zaangażowania, ekspresji romantycznego ducha polskości, a w końcu tęsknot i żalów. To przestrzeń fizyczna i duchowa, obecna w wyobraźni milionów Polaków. Myślimy o Kresach Polski, polskości Kresów, Polakach na Kresach. Sytuujemy się jednoznacznie w pozycji centralnej wobec terenów kresowych, niezwykle ważnych, ale znajdujących się na krańcach naszej kultury. Tymczasem Kresy to nie tylko historia i teraźniejszość Polaków na Ukrainie, Białorusi, Litwie czy Łotwie. Kresy to również teren pogranicza kulturowego w ogóle; miejsce spotkania różnych grup etnicznych i narodowych, różnych wyznań i państwowości. Ich cechą szczególną jest element kryjący się już w samej nazwie. Kresowość bowiem charakteryzuje różne podmioty, nie tylko Polskę i Polaków. Choć Kresy są nam, Polakom, szczególnie bliskie, to nie możemy zapominać, że wiążą się one także nie tylko z pozostałymi narodowościami zamieszkującymi omawianą na łamach czasopisma część Europy Środkowo-Wschodniej, ale również były obecne w dziejach elementem realizacji polityki innego konkurenta Polski – państwa rosyjskiego. To, co my nazywamy Kresami Wschodnimi, dla Rosjan przez długi czas było, i w pewnym sensie nadal jest, Kresami Zachodnimi.