bluuebunny/crossref_metadata_2025 huggingface dataset:
Pott's Puffy Tumor and Intranasal Cocaine Abuse
Authors: Pansini Antonio , Copelli Chiara , Manfuso Alfonso , d’Ecclesia Aurelio , Califano Luigi , Cocchi Roberto
Published: April 2020

Pott's puffy tumor (PPT) is a rare subperiosteal abscess of the frontal bone with osteomyelitis, which most commonly affects adolescents as a complication of frontal sinusitis or head trauma. The Authors describe a case of development of a PPT in a woman who abused of cocaine for at least five years and presented with a gradually enlarging mass of the forehead. The patient was treated surgically through combined endoscopic and open approach and medically with antibiotic therapy. The PPT, as rare complication of intranasal cocaine abuse, was described until now in four patients. Even rare it can be a fearsome complication, making of fundamental importance an early diagnosis and a correct management.
Evaluation of Mandibular Symmetry in Patients With Condylar Osteochondroma Who Underwent Intro-Oral Condylar Resection and Simultaneous Bimaxillary Orthognathic Surgery
Authors: Cao Jian , Shen Shunyao , Liu Zhixu , Dai Jiewen , Wang Xudong
Published: April 2020

Mandibular condylar osteochondroma (OC) can result in facial asymmetry, malocclusion, and temporomandibular joint dysfunction. The authors have previously demonstrated a novel method for conservative condylectomy and simultaneous orthognathic surgery for treatment of mandibular condylar OC. The purpose of this study was to evaluate the immediate improvement and long-term stability of mandibular symmetry in the treatment of condylar OC. Fifty-six patients with unilateral mandibular condylar OC combined with secondary facial asymmetry and malocclusion were enrolled in this retrospective study. The computerized tomography (CT) scans were acquired with the mandible in centric relation (CR) before surgery, 1 week and 12 to 18 months after surgery. The images were reconstructed and processed for the analysis with ProPlan CMF 2.1 software. After defining the skeletal landmarks and the reference planes, the chin deviation, chin rotation and mandibular asymmetry index were calculated. The operations and healing were uneventful and the patients showed no signs of recurrence or temporomandibular joint ankylosis during the follow-up. Facial symmetry was greatly improved right after the surgery in the chin deviation (from 9.2 to 1.7 mm, P < 0.01), chin rotation (from 11.2 to 2.3, P < 0.01) and the asymmetry index of three mandibular landmarks (Go, MF and Sg, all P < 0.01). It also showed a stable result after 12 to 18 months follow-up. We also established a novel measurement method, which showed that the combination of conservative condylectomy via the intraoral approach based on intraoperative navigation and simultaneous orthognathic surgery is effective for improving the facial symmetry when treat the mandibular condylar OC.
Effects of Osteotomy on Hemodynamic Parameters and Depth of Anesthesia in Rhinoplasty Operations
Authors: Gencay Isin , Muluk Nuray Bayar , Kilic Rahmi , Yazici Ilker , Aydin Gulcin , Sencan Ziya , Tozar Mesut , Akcaboy Zeynep Nur , Buyukkocak Unase
Published: April 2020

Background:

Bleeding during rhinoplasty leads to many undesirable effects, such as loss of vision in the surgery area, complications during the procedure, and postoperative complications. The most important effect that increases bleeding is hemodynamic changes during surgery. Considering that osteotomy is the most challenging process in rhinoplasty, this study aimed to examine the hemodynamic changes during osteotomy and changes in the depth of anesthesia.

Methods:

A total of 50 patients, aged 18 to 65 years with an ASA (American Society of Anesthesiology) score of 1 and 2, who underwent osteotomy during rhinoplasty under general anesthesia, were examined retrospectively. After routine monitoring, the patients underwent general anesthesia induction and endotracheal intubation. Before the surgery, they received remifentanil 1 μg/kg as an intravenous bolus followed by 0.5 μg/(kg·min) as intravenous infusion until the end of the surgery. The hemodynamic parameters and depth of anesthesia [bispectral index (BIS) values] of the patients were examined before anesthesia, 10 minutes before osteotomy, during osteotomy, and 10 minutes after osteotomy.

Results:

A significant difference was found in heart rate (beats/min), systolic and diastolic blood pressures (mm Hg), and BIS values of the patients measured before, during, and after osteotomy (P < 0.001). The heart rate, systolic and diastolic blood pressures, and BIS values were significantly higher during osteotomy. Until the 10th minute after osteotomy, all 4 parameters nearly reached the values measured before osteotomy.

Conclusions:

Osteotomy directly affects hemodynamic parameters and depth of anesthesia. Hence, it is of utmost importance that the analgesic need and depth of anesthesia are adequately monitored and adjusted during osteotomy. By suppressing hemodynamic stress responses, the amount of bleeding can be reduced, thus increasing the surgical success and the patient's comfort.
The specific biochemistry of human axilla odour formation viewed in an evolutionary context
Authors: Natsch Andreas , Emter Roger
Published: April 2020

Human body odour is dominated by the scent of specific odourants emanating from specialized glands in the axillary region. These specific odourants are produced by an intricate interplay between biochemical pathways in the host and odour-releasing enzymes present in commensal microorganisms of the axillary microbiome. Key biochemical steps for the release of highly odouriferous carboxylic acids and sulfur compounds have been elucidated over the past 15 years. Based on the profound molecular understanding and specific analytical methods developed, evolutionary questions could be asked for the first time with small population studies: (i) a genetic basis for body odour could be shown with a twin study, (ii) no effect of genes in the human leukocyte antigen complex on the pattern of odourant carboxylic acid was found, and (iii) loss of odour precursor secretion by a mutation in the
ABCC11
gene could explain why a large fraction of the population in the Far East lack body odour formation. This review summarizes what is currently known at the molecular level on the biochemistry of the formation of key odourants in the human axilla. At the same time, we present for the first time the crystal structure of the
N
α
-acyl-aminoacylase, a key human odour-releasing enzyme, thus describing at the molecular level how bacteria on the skin surface have adapted their enzyme to the specific substrates secreted by the human host.

This article is part of the Theo Murphy meeting issue ‘Olfactory communication in humans’.
Lack of coordination and medical disinformation in Canadian self-assessment tools for COVID-19
Authors: Olibris Brieanne , Attaran Amir
Published: April 2020

As SARS-CoV-2 threatens to overwhelm health systems in Canada, it is imperative that provinces are able to plan and manage an effective and reduced risk response. For this response to be most effective, it must reflect an evidence-based, pan-Canadian response. We designed four different prototypical patients with a combination of common COVID-19 symptoms and opportunities for exposure who were made to self-assess using the 10 provincial COVID-19 self-assessment tools on 1 April. These tools were developed to allow individuals to self-triage, allowing health systems direct capacity to testing and care. We assessed the consistency of the self-assessment tools and of the guidance provided to the patients. While the tools generally screen in three areas, the scope of included COVID-19 associated symptoms as well as the opportunities for exposure, and therefore transmission, vary between provinces such that no two provinces screened in the same way. This was, in turn, reflected in the inconsistency in guidance found. A patient with cough who had travelled abroad or had close contact with a confirmed case within 14 days received the most consistent guidance, with remaining patients receiving guidance ranging from mandatory quarantine or self-isolation to being told they did not have COVID-19 symptoms, guidance at odds with medical evidence. Thus, there is not a single, evidence-based Canadian standard of care simply for self-assessment. Without consistency in public health guidance, Canadians cannot appropriately self-isolate to mitigate community transmission, nor can the necessary valid and reliable data be collected to inform critical epidemiological models that help guide pandemic response. If federal and provincial governments are unable to coordinate a response, Parliament must use its available jurisdiction to legislate a duty on both to follow national standards, so as to improve coordination on COVID-19 in coming months.
Neutralizing Antibodies Responses to SARS-CoV-2 in COVID-19 Inpatients and Convalescent Patients
Authors: Wang Xiaoli , Guo Xianghua , Xin Qianqian , Chu Yanhui , Li Jing , Pan Yang , Feng Yingmei , Wang Quanyi
Published: April 2020

Background

COVID-19 is a pandemic with no specific antiviral treatments or vaccines. The urgent needs for exploring the neutralizing antibodies from patients with different clinical characteristics are emerging.

Methods

A total of 117 blood samples were collected from 70 COVID-19 inpatients and convalescent patients. The presence of neutralizing antibody was determined with a modified cytopathogenic assay based on live SARS-CoV-2. The dynamics of neutralizing antibody levels at different with different clinical characteristics were analyzed.

Results

The seropositivity rate reached up to 100.0% within 20 days since onset, and remained 100.0% till day 41-53. The total GMT was 1:163.7 (95% CI, 128.5 to 208.6), and the antibody level was highest during day 31-40 since onset, and then decreased slightly. Individual differences in changes of antibody levels were observed among 8 representative convalescent patients. In multivariate GEE analysis, patients at age of 31-60 and 61-84 had a higher antibody level than those at age of 16-30 (β=1.0518, P=0.0152; β=1.3718, P=0.0020). Patients with a worse clinical classification had a higher antibody titer (β=0.4639, P=0.0227).

Conclusions

The neutralizing antibodies were detected even at the early stage of disease, and a significant response showed in convalescent patients. Moreover, changes on antibody levels ware individual specific.
Discovery of plasma protein biomarkers related to Alzheimer’s disease, sex and APOE genotype
Authors: Laffoon Scott B. , Doecke James D. , Roberts Anne M. , Vance Jennifer A. , Reeves Benjamin D. , Pertile Kelly K. , Rumble Rebecca L. , Fowler Chris J. , Trounson Brett , Ames David , Martins Ralph , Bush Ashley I. , Masters Colin L. , Grieco Paul A. , Dratz Edward A. , Roberts Blaine R.
Published: April 2020

The Australian Imaging and Biomarker Lifestyle (AIBL) study of aging is designed to aid the discovery of biomarkers. The current study aimed to discover differentially expressed plasma proteins that could yield a blood-based screening tool for Alzheimer’s disease. To search for biomarkers and elucidate mechanisms of AD, we immuno-depleted the most abundant plasma proteins and pre-fractionated the remaining proteins by HPLC, prior to two-dimensional gel electrophoresis. The relative levels of approximately 3,400 protein species resolved on the 2D gels were compared using in-gel differential analysis with spectrally resolved fluorescent protein detection dyes (Zdyes™). Here we report on analysis of pooled plasma samples from an initial screen of a sex-matched cohort of 72 probable AD patients and 72 healthy controls from the baseline time point of AIBL. We report significant changes in variants of apolipoprotein E, haptoglobin, α1 anti-trypsin, inter-α trypsin inhibitor, histidine-rich glycoprotein, and a protein of unknown identity. α1 anti-trypsin and α1 anti-chymotrypsin demonstrated plasma concentrations that were dependent onAPOEε4 allele dose. Our analysis also identified an association with the level of Vitamin D binding protein fragments and complement factor I with sex. We then conducted a validation study on individual samples using a targeted LC-MS/MS assay. This study indicates that a peripheral protein signature has potential to aid in the characterization of AD. We also found significant associations of protein levels with APOE genotype, indicating that differences in genotype influence the circulating abundances of proteins other than ApoE.
Regulation of angiotensin converting enzyme 2 (ACE2) in obesity: implications for COVID-19
Authors: Heialy Saba Al , Hachim Mahmood , Senok Abiola , Tayoun Ahmad Abou , Hamoudi Rifat , Alsheikh-Ali Alawi , Hamid Qutayba
Published: April 2020

The ongoing COVID-19 pandemic is caused by the novel coronavirus SARS-CoV-2. Age, smoking, obesity, and chronic diseases such as cardiovascular disease and diabetes have been described as risk factors for severe complications and mortality in COVID-19. Obesity and diabetes are usually associated with dysregulated lipid synthesis and clearance which can initiate or aggravate pulmonary inflammation and injury. It has been shown that for viral entry into the host cell, SARS-CoV-2 utilizes the angiotensin converting enzyme 2 (ACE2) receptors present on the cells. We aimed to characterize how SARS-CoV-2 dysregulates lipid metabolism pathways in the host and the effect of dysregulated lipogenesis on the regulation of ACE2, specifically in obesity. In our study, through the re-analysis of publicly available transcriptomic data, we first found that lung epithelial cells infected with SARS-CoV-2 showed upregulation of genes associated with lipid metabolism, including theSOC3gene which is involved in regulation of inflammation and inhibition of leptin signaling. This is of interest as viruses may hijack host lipid metabolism to allow completion of their viral replication cycles. Furthermore, a mouse model of diet-induced obesity showed a significant increase inAce2expression in the lungs which negatively correlated with the expression of genes that code for sterol response element binding proteins 1 and 2 (SREBP). Suppression ofSrebp1showed a significant increase inAce2expression in the lung. Together our results suggest that the dysregulated lipogenesis and the subsequently high ACE2 expression in obese patients might be the mechanism underlying the increased risk for severe complications in those patients when infected by SARS-CoV-2.
COVID-19 Critical Illness Pathophysiology Driven by Diffuse Pulmonary Thrombi and Pulmonary Endothelial Dysfunction Responsive to Thrombolysis
Authors: Poor Hooman D. , Ventetuolo Corey E. , Tolbert Thomas , Chun Glen , Serrao Gregory , Zeidman Amanda , Dangayach Neha S. , Olin Jeffrey , Kohli-Seth Roopa , Powell Charles A.
Published: April 2020

Critically ill COVID-19 patients have relatively well-preserved lung mechanics despite severe gas exchange abnormalities, a feature not consistent with classical ARDS but more consistent with pulmonary vascular disease. Patients with severe COVID-19 also demonstrate markedly abnormal coagulation, with elevated D-dimers and higher rates of venous thromboembolism. We present four cases of patients with severe COVID-19 pneumonia with severe respiratory failure and shock who demonstrated immediate improvements in gas exchange and/or hemodynamics with systemic tPA.

Subject category

4.6 ICU Management and Outcome
De novo assembly oftrachidermus fasciatusgenome by nanopore sequencing
Authors: Xie Gangcai , Zhang Xu , Lv Feng , Sang Mengmeng , Hu Hairong , Wang Jinqiu , Liu Dong
Published: April 2020

Trachidermus fasciatusis a roughskin sculpin fish widely located at the coastal areas of East Asia. Due to the environmental destruction and overfishing, the populations of this species have been under threat. It is important to have a reference genome to study the population genetics, domestic farming, and genetic resource protection. However, currently, there is no reference genome forTrachidermus fasciatus, which has greatly hurdled the studies on this species. In this study, we proposed to integrate nanopore long reads sequencing, Illumina short reads sequencing and Hi-C methods to thoroughly de novo assemble the genome ofTrachidermus fasciatus. Our results provided a chromosome-level high quality genome assembly with a total length of about 543 Mb, and with N50 of 23 Mb. Based on de novo gene prediction and RNA sequencing information, a total of 38728 genes were found, including 23191 protein coding genes, 2149 small RNAs, 5572 rRNAs, and 7816 tRNAs. Besides, about 23% of the genome area is covered by the repetitive elements. Furthermore, The BUSCO evaluation of the completeness of the assembled genome is more than 96%, and the single base accuracy is 99.997%. Our study provided the first whole genome reference for the species ofTrachidermus fasciatus, which might greatly facilitate the future studies on this species.
capCLIP: a new tool to probe protein synthesis in human cells through capture and identification of the eIF4E-mRNA interactome
Authors: Jensen Kirk B. , Dredge B. Kate , Toubia John , Jin Xin , Iadevaia Valentina , Goodall Gregory J. , Proud Christopher G.
Published: April 2020

Translation of eukaryotic mRNAs starts with binding of the m7G cap to the protein eIF4E followed by recruitment of other translation initiation factors. eIF4E’s essential role in translation suggests the cellular eIF4E-mRNA interactome (or ‘eIF4E cap-ome’) may serve as a faithful proxy of cellular translational activity. Here we describe capCLIP, a novel method to systematically capture and quantify the eIF4E cap-ome. To validate capCLIP, we identified the cap-omes in human cells ± the partial mTORC1 inhibitor rapamycin. As expected, TOP (terminal oligopyrimidine) mRNA representation is systematically reduced in rapamycin-treated cells. capCLIP tag data permits refinement of a 7-nucleotide TOP motif (5′-CUYUYYC-3′). We also apply capCLIP to probe the consequences of phosphorylation of eIF4E, whose function had remained unclear. eIF4E phosphorylation drives an overall reduction in eIF4E-mRNA association; strikingly, mRNAs most sensitive to phosphorylation possess short 5′-UTRs. capCLIP provides a sensitive and comprehensive measure of cellular translational activity. We foresee its application as a high-throughput way to assess translation in contexts not amenable to existing methodologies.
Functionally distinct resident macrophage subsets differentially shape responses to infection in the bladder
Authors: Mariano Livia Lacerda , Rousseau Matthieu , Varet Hugo , Legendre Rachel , Gentek Rebecca , Saenz Coronilla Javier , Bajenoff Marc , Perdiguero Elisa Gomez , Ingersoll Molly A
Published: April 2020

Resident macrophages are abundant in the bladder, playing key roles in immunity to uropathogens. Yet, whether they are heterogeneous, where they come from, and how they respond to infection remain largely unknown. We identified two macrophage subsets in mouse bladders, MacM in the muscle and MacL in the lamina propria, with distinct protein expression and transcriptomes. Using a urinary tract infection model, we validated our transcriptomic analyses, finding that MacM macrophages phagocytosed more bacteria and polarized to a more anti-inflammatory profile, whereas the MacL subset died rapidly during infection. During resolution, monocyte-derived cells contributed to tissue-resident macrophage pools and both subsets acquired transcriptional profiles distinct from naïve macrophages. Depletion of these altered macrophages resulted in the induction of a type 1 biased immune response to a second urinary tract infection, improving bacterial clearance. Our study uncovers the biology of resident macrophages and their response to an exceedingly common infection in a largely overlooked organ, the bladder.
Macrophage Function is Regulated by NPM1-mediated 2’-O-methylation
Authors: Sportoletti Paolo , Nachmani Daphna , Riccardi Luisa , Khanna-Gupta Arati , Chen Jian , Marra Andrea , Berliner Nancy , Clohessy John G. , Pandolfi Pier Paolo
Published: April 2020

TheNPM1gene is frequently a target of genetic alteration in hematological tumors, particularly of the myeloid lineage. Complete inactivation ofNpm1in the mouse disrupts primitive hematopoiesis and results in embryonic lethality.Npm1heterozygosity produces features similar to those of MDS that progress to overt leukemia, and specific point mutations ofNpm1lead to bone marrow failure due to loss of hematopoietic stem cells. However, little is known about NPM1’s role in mature, differentiated cells. Here we generated a conditional mouse mutant to inactivateNpm1across the myelomonocytic lineage, and investigated its ability to influence macrophage maturation and function. We found thatNpm1is not required to maintain macrophage viability, while its loss in mature macrophages reduces production of reactive oxygen species, chemotactic properties and phagocytic capacity. Taking advantage of our recently establishedNpm1D180delmouse model of ribosome dysfunction and hematological disease, we identify cellular translation and rRNA 2’-O-methlyation as a crucial element in controlling macrophage function. These analyses demonstrate a role forNpm1in adult immune cells, and reveal the importance of translation regulation in macrophage function.

Statement of significance

Macrophages are a major component of the immune response to various insults including to cancer. Here we show that NPM1, the most frequently mutated gene in acute myeloid leukemia, displays a critical role in macrophage function, and we identify ribosome deregulation as one of the underlying mechanisms.
A Factor Model Analysis of the Australian Economy and the Effects of Inflation Targeting
Authors: Hartigan Luke , Morley James
Published: April 2020

Based on a dynamic factor model for a data set with more than 100 variables, we find that macroeconomic fluctuations in Australia can be largely captured by just two common factors. However, the factor structure changed soon after the introduction of inflation targeting in the 1990s, resulting in a large reduction in cross‐sectional variation related to these common factors. Estimates from a block‐exogenous factor‐augmented vector autoregressive model suggest that the transmission and responsiveness of monetary policy also changed, with policy both more effective and responsive to the potential inflationary impacts of shocks following the introduction of inflation targeting.
Altered testicular cell type composition in males of two outbred mouse lines selected for high fertility
Authors: Michaelis Marten , Sobczak Alexander , Ludwig Carolin , Marvanová Hana , Langhammer Martina , Schön Jennifer , Weitzel Joachim M.
Published: April 2020

Background

Recently we described two outbred mouse lines which have been selected for high fertility. These mouse models doubled the number of offspring per litter.

Objectives

Although selected for a primarily female‐trait of high fertility (increased litter size), we were interested whether also males of the fertility lines show differences within their reproductive organs.

Materials and methods

We investigated males from two outbred mouse lines which have been selected for the phenotype “high fertility” for more than 170 generations. In the present study, we analysed the testicular cell type composition by flow cytometry. We further investigated the weights of reproductive organs, histomorphometry of testis as well as studied sperm motility parameters using a thermal stress assay as well as a sperm hyperactivation assay.

Results

Here, we describe that males of the fertility line (FL) 1 show an increased percentage of diploid cells within the testis. Flow cytometric analysis identified this enlarged cell population as Leydig cells. Testis weights were unaffected whereas the weights of seminal vesicles of FL1 and FL2 were increased compared to Ctrl bucks. FL2 males show decreased diameter of tubulus seminiferi and an enhanced spermatid/Sertoli cell index. Sperm motility parameters of FL1 and Ctrl males are initially indistinguishable but FL1 spermatozoa show a better performance in a thermal stress experiment over a 5 hours observation period.

Discussion

These data indicate that although selected for a primarily female‐trait of high fertility also males from the fertility lines are effected by defined alterations in their reproductive organs.

Conclusion

Some of these alterations are FL1‐specific others are FL2‐associated, indicating that different molecular strategies warrant the high‐fertility phenotype on the female as well as on the male side.
Prolonged therapeutic effects of photoactivated adipose‐derived stem cells following ischaemic injury
Authors: Fan Xin , Li Kai , Zhu Luochen , Deng Xin , Feng Ziqian , Xu Chunrong , Liu Sijing , Wu Jianbo
Published: April 2020

Aim

Adipose‐derived stem cells (ASCs) therapies are emerging as a promising approach to therapeutic angiogenesis. Therapeutic persistence and reduced primitive stem cell function following cell delivery remains a critical hurdle for the clinical translation of stem cells in current approaches.

Methods

Cultured ASCs were derived from subcutaneous white adipose tissue isolated from mice fed a normal diet (ND). Unilateral hindlimb ischaemia model was induced in high‐fat diet (HFD)‐fed mice by femoral artery interruption, after which photoactivated and non‐light‐treated ASCs were injected into the tail vein of mice. Laser Doppler imaging was conducted to measure the blood flow reperfusion. Capillary density was measured in the ischaemic gastrocnemius muscle. mRNA levels of angiogenic factors were determined by reverse‐transcription polymerase chain reaction. Flow cytometry was used to determine the characterization of ASCs and endothelial progenitor cell (EPC). Human ASCs secretomes were analysed by liquid chromatography tandem mass spectrometry.

Results

Our study demonstrated that photoactivated ND‐ASCs prolonged functional blood flow perfusion and increased ASCs‐derived EPC and neovascularization 38 days after ligation, when compared with saline‐treated controls. Profiling analysis in ischaemic muscles showed upregulation of genes associated with pro‐angiogenic factors after injection of photoactivated ND‐ASCs when compared with the non‐light‐treated ASCs or saline treated HFD mice. Mass spectrometry revealed that light‐treated ASCs conditioned medium retained a more complete pro‐angiogenic activity with significant upregulation of angiogenesis related proteins.

Conclusion

Our data demonstrates that photoactivated ND‐ASCs improve blood flow recovery and their injection may prove to be a useful strategy for the prevention and treatment of diabetic peripheral arterial disease.
Ensiling characteristics of total mixed ration prepared with local feed resources in Mozambique and their effects on nutrition value and milk production in Jersey dairy cattle
Authors: Du Zhumei , Yamasaki Seishi , Oya Tetsuji , Nguluve Damiao , Tinga Benedito , Macome Felicidade , Cai Yimin
Published: April 2020

To effectively utilize total mixed ration (TMR) prepared with locally available feed resources, we studied the nutritional value and milk production in Jersey dairy cattle fed a local general diet (LGD) and fermented TMR in Mozambique. Ten head of Jersey dairy cattle with 337 ± 19.8 kg body weight, aged 3–4 years in mid location were used in this study. The LGD diet was designed following the general feeding method of local smallholding farms; it contained native grass, Napier grass, wheat bran, and mineral–vitamin mix. Fermented TMR was prepared using Napier grass, corn bran, wheat bran, formula feed, and mineral–vitamin mix. Fermented TMR was preserved as good quality, with a relatively low pH and high lactic acid content. Compared to LGD, fermented TMR significantly improved the dry matter intake and digestibility in dairy cattle. Milk yield was significantly higher in dairy cattle fed with TMR than in those fed with LGD, by 3.75 L/d; milk quality was not significantly different between treatments. The results confirmed that LGD had a low dry matter intake and milk yield, and fermented TMR prepared with local feed resources can attain good quality and improve milk yield in dairy cattle in Mozambique.
Long‐term farming systems and last crop sown shape the species and functional composition of the arable weed seed bank
Authors: Rotchés‐Ribalta Roser , Sans Francesc Xavier , Mayer Jochen , Mäder Paul
Published: April 2020

Questions: The assembly of arable weed communities is the result of local filtering by agricultural management and crop competition. Therefore, soil seed banks can reflect the effects of long‐term cumulative field management and crop sequences on weed communities. Moreover, soil seed banks provide strong estimates of future weed problems but also of potential arable plant diversity and associated ecological functions. For this, we evaluated the effects of different long‐term farming systems under the same crop rotation sequence on the abundance, diversity and community assembly of weed seed bank, as well as on the functional diversity and composition.

Location: DOK (biodynamic [D], bioorganic [O], conventional [K]) long‐term trial, Therwil, Switzerland.

Methods: The effects of long‐term contrasted farming systems (i.e., biodynamic, organic, conventional, mineral and unfertilised systems) and last crop sown (i.e., wheat and maize) were evaluated on different indicators of species and functional diversity and composition of the weed soil seed bank.

Results: The results showed significant influences of 40 years of contrasted farming systems on the diversity and composition of the seed bank, with higher diversities being found in unfertilised and organic farming systems, but also higher abundances than those found under conventional systems. Organic farming also allowed higher functional richness, dispersion and redundancy. Different farming systems triggered shifts in species and functional assemblies.

Conclusions: The results highlight the importance of organic management for the maintenance of a diverse arable plant community and its functions. However, such results emphasise the need for appropriate yearly management to reduce the abundance of settled weediness and prevent affecting crop production. The farm management filtered community composition based on functional traits. Although the soil seed bank buffers the long‐term farming and crop sequence, the last crop sown and, thus, the yearly management were important determinants of seed bank composition.
I (dis)like the way you (dis)like them: The role of extended contact on social distance and attitudes towards the ingroup
Authors: Bagci Sabahat Cigdem , Stathi Sofia , Vezzali Loris , Turnuklu Abbas , Piyale Zeynep Ecem
Published: April 2020

While extended intergroup contact has been commonly studied in the context of prejudice reduction, less is known about its implications for processes related to the ingroup. Through three correlational and one experimental studies (total N = 897) conducted in two different intergroup contexts (Turkey and United Kingdom), we investigated whether extended intergroup contact relates to social distance and attitudes towards ingroup members as a function of outgroup attitudes. We also investigated ingroup identification and perceived ingroup morality as potential mediators in these associations. Correlational studies demonstrated that especially when outgroup attitudes were more negative, participants’ positive (but not negative) extended contact was related to a more negative evaluation of the ingroup; whereas when outgroup attitudes were more positive, extended contact was associated with positive attitudes towards the ingroup. We found experimental evidence for the suggested relationships in relation to ingroup social distance. Findings are discussed in the light of vicarious dissonance theory and deprovincialization hypothesis.
REV‐ERBα activates the mTOR signalling pathway and promotes myotubes differentiation
Authors: Dadon‐Freiberg Maayan , Chapnik Nava , Froy Oren
Published: April 2020

Background Information

Mammalian target of rapamycin (mTOR) complex 1 (mTORC1) is a master regulator of cell and whole‐body energy homoeostasis. REV‐ERBα is a nuclear receptor that plays an important role in metabolism. While mTORC1 activation is necessary for muscle differentiation, the role of REV‐ERBα is less clear.

Results

We studied the effect of REV‐ERBα overexpression and silencing as well as mTORC1 activation and inhibition on the differentiation of C2C12 myoblasts to myotubes. mTOR, myogenin and REV‐ERBα were induced during differentiation of myoblasts into myotubes. REV‐ERBα was found to activate mTORC1 during the differentiation process even in the absence of the differentiation medium. This activation was presumably through the downregulation of the expression of TSC1, an mTORC1 inhibitor.

Conclusion

Herein we show that REV‐ERBα promotes myoblasts differentiation via the activation of the mTORC1 signalling pathway.

Significance

REV‐ERBα modulation can activate mTORC1 signalling and promote myoblasts differentiation.
Tyrosine kinase inhibitors induce alternative spliced BCR‐ABLIns35bp variant via inhibition of RNA polymerase II on genomic BCR‐ABL
Authors: Yuda Junichiro , Odawara Jun , Minami Mariko , Muta Tsuyoshi , Kohno Kentaro , Tanimoto Kazuki , Eto Tetsuya , Shima Takahiro , Kikushige Yoshikane , Kato Koji , Takenaka Katsuto , Iwasaki Hiromi , Minami Yosuke , Ohkawa Yasuyuki , Akashi Koichi , Miyamoto Toshihiro
Published: April 2020

To elucidate dynamic changes in native BCR‐ABL and alternatively spliced tyrosine kinase inhibitor (TKI)‐resistant but function‐dead BCR‐ABLIns35bp variant, following commencement or discontinuation of TKI therapy, each transcript was serially quantified in patients with chronic myeloid leukemia (CML) by deep sequencing. Because both transcripts were amplified together using conventional PCR system for measuring International Scale (IS), deep sequencing method was used for quantifying such BCR‐ABL variants. At the initial diagnosis, 7 of 9 patients presented a small fraction of cells possessing BCR‐ABLIns35bp, accounting for 0.8% of the total IS BCR‐ABL, corresponding to actual BCR‐ABLIns35bp value of 1.1539% IS. TKI rapidly decreased native BCR‐ABL but not BCR‐ABLIns35bp, leading to the initial increase in the proportion of BCR‐ABLIns35bp. Thereafter, both native BCR‐ABL and BCR‐ABLIns35bp gradually decreased in the course of TKI treatment, whereas small populations positive for TKI‐resistant BCR‐ABLIns35bp continued fluctuating at low levels, possibly underestimating the molecular response (MR). Following TKI discontinuation, sequencing analysis of 54 patients revealed a rapid relapse, apparently derived from native BCR‐ABL+ clones. However, IS fluctuating at low levels around MR4.0 marked a predominant persistence of cells expressing function‐dead BCR‐ABLIns35bp, suggesting that TKI resumption was unnecessary. We clarified the possible mechanism underlying mis‐splicing BCR‐ABLIns35bp, occurring at the particular pseudo‐splice site within intron8, which can be augmented by TKI treatment through inhibition of RNA polymerase II phosphorylation. No mutations were found in spliceosomal genes. Therefore, monitoring IS functional BCR‐ABL extracting BCR‐ABLIns35bp would lead us to a correct evaluation of MR status, thus determining the adequate therapeutic intervention.
Clinical and functional consequences of anti-properdin autoantibodies in patients with lupus nephritis
Authors: Radanova M , Mihaylova G , Ivanova D , Daugan M , Lazarov V , Roumenina L , Vasilev V
Published: April 2020

Properdin is the only positive regulator of the complement system. In this study, we characterize the prevalence, functional consequences and disease associations of autoantibodies against properdin in a cohort of patients with autoimmune disease systemic lupus erythematosus (SLE) suffering from lupus nephritis (LN). We detected autoantibodies against properdin in plasma of 22·5% of the LN patients (16 of 71) by enzyme-linked immunosorbent assay (ELISA). The binding of these autoantibodies to properdin was dose-dependent and was validated by surface plasmon resonance. Higher levels of anti-properdin were related to high levels of anti-dsDNA and anti-nuclear antibodies and low concentrations of C3 and C4 in patients, and also with histological signs of LN activity and chronicity. The high negative predictive value (NPV) of anti-properdin and anti-dsDNA combination suggested that patients who are negative for both anti-properdin and anti-dsDNA will not have severe nephritis. Immunoglobulin G from anti-properdin-positive patients’ plasma increased the C3b deposition on late apoptotic cells by flow cytometry. Nevertheless, these IgGs did not modify substantially the binding of properdin to C3b, the C3 convertase C3bBb and the pro-convertase C3bB, evaluated by surface plasmon resonance. In conclusion, anti-properdin autoantibodies exist in LN patients. They have weak but relevant functional consequences, which could have pathological significance.
Endoscopic management of walled‐off pancreatic necrosis
Authors: Yasuda Ichiro , Takahashi Kosuke
Published: April 2020

Walled‐off pancreatic necrosis (WON) can develop in the late phase of necrotizing pancreatitis. When the WON is accompanied by an infection in the necrotic bed, it becomes a life‐threatening complication. Open necrosectomy with drainage has been the standard treatment; however, it is associated with a significant morbidity and high mortality. Therefore, minimally invasive therapeutic alternatives are in demand. Recently, a new treatment algorithm for necrotizing pancreatitis, known as the step‐up approach, has been proposed. The initial report on it consisted of percutaneous drainage followed by, if necessary, a minimally invasive retroperitoneal necrosectomy. However, the endoscopic step‐up approach, which consists of EUS‐guided transluminal drainage followed by, if necessary, endoscopic necrosectomy, was later introduced. Recent studies have suggested that an endoscopic step‐up approach might be more advantageous than a minimally invasive surgical step‐up approach. A lumen apposing metal stent (LAMS) with a cautery‐enhanced delivery system is currently preferred over the conventional plastic stents for endoscopic interventions, because it decreases the technical difficulty of the procedure and may obviate the need for an adjunctive debridement procedure. However, some recent findings suggest that LAMS could be associated with a higher risk of stent‐related complications than conventional plastic stents, especially in patients with long‐term placement. Therefore, early removal of LAMS at 3 weeks post‐intervention is proposed if the WON is resolved on CT examination. Thus, endoscopic interventions have emerged as a key player in the management of WON. However, multidisciplinary treatment approaches should be considered because the endoscopic approach has limitations in treating complicated WON.
Prognosis of patients eligible for dapagliflozin in acute heart failure
Authors: Carballo Sebastian , Stirnemann Jérôme , Garin Nicolas , Darbellay Farhoumand Pauline , Serratrice Jacques , Carballo David
Published: April 2020

Background

Dapagliflozin, a sodium‐glucose cotransporter 2 inhibitor, was shown in the DAPA‐HF study to reduce the risk of worsening heart failure or death in symptomatic patients with left ejection fraction <40%, irrespective of diabetes. The aim of this study was to evaluate eligibility status for dapagliflozin in non‐selected patients hospitalized for acute decompensated heart failure (ADHF), as well as prognostic implications of this status.

Materials and methods

Analysis of 815 patients recruited in a prospective cohort of acute heart failure at the University Hospitals of Geneva, consisting of consecutive patients admitted with ADHF. Eligibility for dapagliflozin was determined using criteria described DAPA‐HF.

Results

Of 815 patients, 220 (27%) were eligible for dapagliflozin treatment. In survival analysis, patients who were eligible for dapagliflozin had better clinical outcomes with respect to all‐cause mortality and rehospitalization as compared to those who were not eligible. In multivariate analysis, the hazard ratio for all‐cause mortality or readmission in patients eligible for dapagliflozin was 0.82 (95% CI 0.68‐0.999, P = .049) as compared to the non‐eligible.

Conclusions

Using DAPA‐HF criteria, only 27% of non‐selected patients admitted for ADHF are theoretically eligible for dapagliflozin. This eligibility for dapagliflozin is associated with better outcomes. Further evaluation of the benefits of dapagliflozin in selected HF patients may be of interest. This may have implications for selection criteria in future randomized effectiveness studies.
The influence of COMT rs4680 on functional connectivity in healthy adults: A systematic review
Authors: Morris Kim A. , Grace Sally A. , Woods Will , Dean Brian , Rossell Susan L.
Published: April 2020

The aim of this systematic review was to qualitatively synthesise the available research that investigated the influence of COMT genotype at SNP rs4680 on both task‐based and resting‐state connectivity in healthy adults. Thirty‐five studies were identified that met inclusion criteria. Of the included studies, 20 studies reported resting‐state findings and 16 studies reported task‐based findings (emotion‐processing, memory, working memory, reward‐based learning and executive function). Studies were highly heterogeneous but an overall trend towards an association of the Val allele with greater resting‐state connectivity and the Met allele with greater task‐based connectivity is reported. A possible interpretation of current findings is discussed, whereby the Val allele is associated with improved cognitive flexibility allowing integration of novel relevant stimuli, and the Met allele allows improved sustained attention and targeted neural processing, particularly between limbic regions and prefrontal cortex. The most promising brain regions implicated in a COMT genotype influence on functional connectivity include prefrontal regions, amygdala and hippocampus.
Astrocytic equilibrative nucleoside transporter type 1 upregulations in the dorsomedial and dorsolateral striatum distinctly coordinate goal‐directed and habitual ethanol‐seeking behaviours in mice
Authors: Hong Sa‐Ik , Bullert Amanda , Baker Matthew , Choi Doo‐Sup
Published: April 2020

Two distinct dorsal striatum regions, dorsomedial striatum (DMS) and dorsolateral striatum (DLS), are attributed to conditioned goal‐directed and habitual reward‐seeking behaviours, respectively. Previously, our study shows that the ethanol‐sensitive adenosine transporter, equilibrative nucleoside transporter 1 (ENT1), regulates ethanol‐drinking behaviours. Although ENT1 is expressed in both neurons and astrocytes, astrocytic ENT1 is thought to regulate adenosine levels in response to ethanol. However, the role of DMS and DLS astrocytic ENT1 in goal‐directed and habitual ethanol‐seeking is not well known. Here, we identified whether the upregulation of astrocytic ENT1 in the DMS and DLS differentially regulates operant seeking behaviours towards the 10% sucrose (10S); 10% ethanol and 10% sucrose (10E10S); and 10% ethanol (10E) in mice. Using 4 days of random interval (RI), mice exhibited habitual seeking for 10S, but goal‐directed seeking towards 10E10S. Using the same mice conditioned with 10E10S, we examined 10E‐seeking behaviour on a fixed ratio (FR) for 6 days and RI for 8 days. On the other hand, during FR and the first 4 days of RI schedules, mice showed goal‐directed seeking for 10E, whereas mice exhibited habitual seeking for 10E during the last 4 days of RI schedule. Interestingly, DMS astrocytic ENT1 upregulation promotes shift from habitual to goal‐directed reward‐seeking behaviours. By contrast, DLS astrocytic ENT1 upregulation showed no effects on behavioural shift. Taken together, our findings demonstrate that DMS astrocytic ENT1 contributes to reward‐seeking behaviours.
Top‐down modulation of neural envelope tracking: The interplay with behavioral, self‐report and neural measures of listening effort
Authors: Decruy Lien , Lesenfants Damien , Vanthornhout Jonas , Francart Tom
Published: April 2020

When listening to natural speech, our brain activity tracks the slow amplitude modulations of speech, also called the speech envelope. Moreover, recent research has demonstrated that this neural envelope tracking can be affected by top‐down processes. The present study was designed to examine if neural envelope tracking is modulated by the effort that a person expends during listening. Five measures were included to quantify listening effort: two behavioral measures based on a novel dual‐task paradigm, a self‐report effort measure and two neural measures related to phase synchronization and alpha power. Electroencephalography responses to sentences, presented at a wide range of subject‐specific signal‐to‐noise ratios, were recorded in thirteen young, normal‐hearing adults. A comparison of the five measures revealed different effects of listening effort as a function of speech understanding. Reaction times on the primary task and self‐reported effort decreased with increasing speech understanding. In contrast, reaction times on the secondary task and alpha power showed a peak‐shaped behavior with highest effort at intermediate speech understanding levels. With regard to neural envelope tracking, we found that the reaction times on the secondary task and self‐reported effort explained a small part of the variability in theta‐band envelope tracking. Speech understanding was found to strongly modulate neural envelope tracking. More specifically, our results demonstrated a robust increase in envelope tracking with increasing speech understanding. The present study provides new insights in the relations among different effort measures and highlights the potential of neural envelope tracking to objectively measure speech understanding in young, normal‐hearing adults.
Enzymology of the pathway for ATP production by arginine breakdown
Authors: Pols Tjeerd , Singh Shubham , Deelman‐Driessen Cecile , Gaastra Bauke F. , Poolman Bert
Published: April 2020

In cells, the breakdown of arginine to ornithine and ammonium ion plus carbon dioxide is coupled to the generation of metabolic energy in the form of ATP. The arginine breakdown pathway is minimally composed of arginine deiminase, ornithine transcarbamoylase, carbamate kinase, and an arginine/ornithine antiporter; ammonia and carbon dioxide most likely diffuse passively across the membrane. The genes for the enzymes and transporter have been cloned and expressed, and the proteins have been purified from Lactococcus lactis IL1403 and incorporated into lipid vesicles for sustained production of ATP. Here, we study the kinetic parameters and biochemical properties of the individual enzymes and the antiporter, and we determine how the physicochemical conditions, effector composition, and effector concentration affect the enzymes. We report the KM and VMAX values for catalysis and the native oligomeric state of all proteins, and we measured the effect of pathway intermediates, pH, temperature, freeze–thaw cycles, and salts on the activity of the cytosolic enzymes. We also present data on the protein‐to‐lipid ratio and lipid composition dependence of the antiporter.