bluuebunny/crossref_metadata_2025 huggingface dataset:
Exercise twice‐a‐day potentiates markers of mitochondrial biogenesis in men
Authors: Andrade‐Souza Victor Amorim , Ghiarone Thaysa , Sansonio Andre , Santos Silva Kleiton Augusto , Tomazini Fabiano , Arcoverde Lucyana , Fyfe Jackson , Perri Enrico , Saner Nicholas , Kuang Jujiao , Bertuzzi Romulo , Leandro Carol Gois , Bishop David John , Lima‐Silva Adriano Eduardo
Published: December 2019

Endurance exercise begun with reduced muscle glycogen stores seems to potentiate skeletal muscle protein abundance and gene expression. However, it is unknown whether this greater signaling responses is due to performing two exercise sessions in close proximity—as a first exercise session is necessary to reduce the muscle glycogen stores. In the present study, we manipulated the recovery duration between a first muscle glycogen‐depleting exercise and a second exercise session, such that the second exercise session started with reduced muscle glycogen in both approaches but was performed either 2 or 15 hours after the first exercise session (so‐called “twice‐a‐day” and “once‐daily” approaches, respectively). We found that exercise twice‐a‐day increased the nuclear abundance of transcription factor EB (TFEB) and nuclear factor of activated T cells (NFAT) and potentiated the transcription of peroxisome proliferator‐activated receptor‐ɣ coactivator 1‐alpha (PGC‐1α), peroxisome proliferator‐activated receptor‐alpha (PPARα), and peroxisome proliferator‐activated receptor beta/delta (PPARβ/δ) genes, in comparison with the once‐daily exercise. These results suggest that part of the elevated molecular signaling reported with previous “train‐low” approaches might be attributed to performing two exercise sessions in close proximity. The twice‐a‐day approach might be an effective strategy to induce adaptations related to mitochondrial biogenesis and fat oxidation.
Ascidian caveolin induces membrane curvature and protects tissue integrity and morphology during embryogenesis
Authors: Bhattachan Punit , Rae James , Yu Haiyan , Jung WooRam , Wei Jiankai , Parton Robert G. , Dong Bo
Published: December 2019

Cell morphology and tissue integrity are essential for embryogenesis. Caveolins are membrane proteins that induce the formation of surface pits called caveolae that serve as membrane reservoirs for cell and tissue protection during development. In vertebrates, caveolin 1 (Cav1) and caveolin 3 (Cav3) are required for caveola formation. However, the formation of caveola and the function of caveolins in invertebrates are largely unknown. In this study, three caveolins, Cav‐a, Cav‐b, and CavY, are identified in the genome of the invertebrate chordate Ciona spp. Based on phylogenetic analysis, Cav‐a is found to be closely related to the vertebrate Cav1 and Cav3. In situ hybridization shows that Cav‐a is expressed in Ciona embryonic notochord and muscle. Cell‐free experiments, model cell culture systems, and in vivo experiments demonstrate that Ciona Cav‐a has the ability to induce membrane curvature at the plasma membrane. Knockdown of Cav‐a in Ciona embryos causes loss of invaginations in the plasma membrane and results in the failure of notochord elongation and lumenogenesis. Expression of a dominant‐negative Cav‐a point mutation causes cells to change shape and become displaced from the muscle and notochord to disrupt tissue integrity. Furthermore, we demonstrate that Cav‐a vesicles show polarized trafficking and localize at the luminal membrane during notochord lumenogenesis. Taken together, these results show that the invertebrate chordate caveolin from Ciona plays crucial roles in tissue integrity and morphology by inducing membrane curvature and intracellular vesicle trafficking during embryogenesis.
Outside‐in regulation of the readily releasable pool of synaptic vesicles by α2δ‐1
Authors: Martínez San Segundo Pablo , Terni Beatrice , Burgueño Javier , Monroy Xavier , Dordal Albert , Merlos Manuel , Llobet Artur
Published: December 2019

The readily releasable pool (RRP) of synaptic vesicles is a key determinant of phasic neurotransmission. Although the size of the RRP is tightly regulated by intracellular factors, there is little evidence for its modification by extracellular signals. By studying the homogeneous population of synapses present in autaptic microcultures, we show that pregabalin, a prototypical gabapentinoid, decreases the effective RRP size. Simultaneous imaging of presynaptic calcium influx and recording of postsynaptic responses shows that the effect is not related to a reduction of calcium entry. The main cause is the impairment of the functional coupling among N‐type calcium channels and the RRP, resembling an increase of intracellular mobile calcium buffers. The ectodomain of neurexin‐1α shows a similar action to pregabalin, acting as an endogenous ligand of α2δ‐1 that reduces the RRP size without affecting presynaptic calcium influx. The regulatory actions described for pregabalin and the ectodomain of neurexin‐1α are mutually exclusive. The overexpression of α2δ‐1 enhances the effect of pregabalin and the ectodomain of neurexin‐1α on neurotransmission by decreasing their effective concentration. In contrast, knockdown of α2δ‐1 causes a profound inhibition of synaptic transmission. These observations prompt to consider α2δ‐1 as an outside‐in signaling platform that binds exogenous and endogenous cues for regulating the coupling of voltage‐gated calcium channels to synaptic vesicles.
Pathologic arterial changes in neurovascularly intact Gartland III supracondylar humerus fractures: a pilot study
Authors: Ho Christine A. , Podeszwa David A. , Riccio Anthony I. , Wimberly Robert L. , Ramo Brandon A. , Yang Mary , Patel Surekha
Published: December 2019

This pilot study was performed to describe changes in arterial flow in completely displaced neurovascularly intact Gartland III pediatric supracondylar humerus fractures using Duplex ultrasonography. This is a prospective study of 11 Gartland type III supracondylar humerus fractures with no cortical continuity but with palpable radial pulse and normal neurologic examination. Duplex ultrasonography was performed on injured and uninjured arms, both preoperatively and postpinning, and interpreted by a board-certified pediatric radiologist. Degree of artery stenosis and peak systolic velocity (PSV) of arterial flow were recorded from the duplex. Ultrasound wrist/brachial indexes (WBI) were calculated using the higher value of the radial/brachial or the ulnar/brachial index. Only three patients had normal Duplexes without stenosis and with flow comparable in the brachial, radial, and ulnar arteries of the affected arm, compared to the unaffected arm, both preoperatively and postpinning. One group of six patients had brachial artery stenosis at the fracture site when compared to the artery proximal to the fracture site, increased PSV at the fracture site compared to proximal to the fracture site, and the WBI was variable when compared to the contralateral side. A third group of two patients also had brachial artery stenosis at the fracture site but had decreased PSV and decreased WBI compared to the contralateral side. Type III supracondylar humerus patients with a normal neurovascular examination may have abnormal Duplex ultrasonography with brachial artery stenosis and elevated peak systolic velocity preoperatively although distal flow remains comparable to the contralateral side. Level of evidence: prognostic – Level II.
Follicular Eruption With Folliculotropic Lymphocytic Infiltrates Associated With Iatrogenic Immunosuppression: Report and Study of 3 Cases, and Review of the Literature
Authors: Avitan-Hersh Emily , Dias-Polak David , Ramon Michal , Sahar Dvora , Magen Daniella , Pollack Shirley , Bergman Reuven
Published: December 2019

Background:

Several cases of folliculotropic mycosis fungoides, associated with immunosuppressive therapy, including calcineurin inhibitors, have been reported in solid organ transplant patients. We have encountered 3 patients on immunosuppressive therapy who developed follicular eruptions with folliculocentric infiltrates of nonatypical lymphocytes.

Objective:

To characterize these follicular eruptions and review the literature.

Methods:

Three patients, aged 7–15 years, who were treated with systemic immunosuppressive therapy developed follicular eruptions characterized histopathologically by folliculocentric lymphocytic infiltrates. These were studied clinically, histopathologically, immunophenotypically, and molecularly for T-cell receptor (TCR) gene rearrangement.

Results:

All 3 cases were characterized histopathologically by folliculocentric infiltrates of nonatypical CD3+ T lymphocytes with variable follicular exocytosis. Two cases also showed follicular mucinosis. Marked reduction in CD7+ staining, and marked predominance of CD4+ cells over CD8+ cells was observed in all 3 cases. The TCR gene rearrangement studies were monoclonal in 2 cases. Oral calcineurin inhibitors (2 cyclosporine A and 1 tacrolimus) were part of the therapeutic regimen in all 3 patients. Their cessation along with local corticosteroid creams in 2 patients, and phototherapy with oral acitretin in one patient, was associated with complete clinical remission.

Conclusions:

Patients undergoing systemic immunosuppressive therapy that includes calcineurin inhibitors might develop follicular eruption with some immunophenotypical variations and a monoclonal TCR gene rearrangement but lack sufficient cytomorphological features of folliculotropic mycosis fungoides. Altering the immunosuppressive agent including calcineurin inhibitors may result in regression of the eruptions.
Circulating Mesencephalic Astrocyte-Derived Neurotrophic Factor Negatively Correlates With Atrial Apoptosis in Human Chronic Atrial Fibrillation
Authors: Wang Changhui , Yu Shujun , Bao Qin , Qiang Weimin , Wu Chaoran , Zhang Chengxin , Jiang Yan , Cai Yongping , Huang Dake , Chen Ying , Hou Chao , Wang Dong
Published: December 2019

Atrial apoptosis has been found to be majorly involved in the pathogenesis of human atrial fibrillation (AF). Mesencephalic astrocyte-derived neurotrophic factor exerts an antiapoptotic effect for multiple cell types. However, the correlation between MANF and atrial apoptosis in AF is still undefined. In this study, 59 patients with valvular or congenital heart disease were divided into 2 groups: AF group and sinus rhythm (SR) group. We found that the apoptotic atrial myocytes in the right atrial appendage tissues of the AF group were significantly more than those of the SR group, whereas mRNA and protein levels of MANF in the AF group were significantly down-regulated compared with those in the SR group. The serum MANF in patients with AF was markedly lower than that in patients with SR, which was inversely correlated with atrial apoptosis in patients with AF. In addition, the AF group had the greater inflammation and endoplasmic reticulum stress compared with the SR group. These findings suggest that MANF downregulation may lead to more atrial apoptosis in human chronic AF, indicating MANF as a potential therapeutic agent in AF treatment.
Isavuconazole in Hematological Patients: Results of a Real-Life Multicentre Observational Seifem Study
Authors: Cattaneo Chiara , Busca Alessandro , Gramegna Doriana , Farina Francesca , Candoni Anna , Piedimonte Monica , Fracchiolla Nicola , Pagani Chiara , Principe Maria Ilaria Del , Tisi Maria Chiara , Offidani Massimo , Fanci Rosa , Ballanti Stelvio , Spolzino Angelica , Criscuolo Marianna , Marchesi Francesco , Nadali Gianpaolo , Delia Mario , Picardi Marco , Sciumé Margherita , Mancini Valentina , Olivieri Attilio , Tumbarello Mario , Rossi Giuseppe , Pagano Livio
Published: December 2019

Invasive fungal diseases (IFDs) remain a major clinical issue in patients with hematological malignancies (HMs). To confirm the efficacy and safety of the new azole isavuconazole (ISV) in a clinical care setting, we planned a multicenter retrospective study; we collected data on all possible/probable/proven IFDs in patients with HMs treated with ISV in 17 centers. Between July 2016 and November 2018, 128 patients were enrolled, and 122 were fully evaluable. ISV was employed as the 1st line therapy in 43 (35%) patients and as a subsequent therapy in 79 (65%) patients. The response rate was 82/122 patients (67.2%); it was similar when using ISV as a 1st or 2nd line treatment (60.5% vs 70.9%, respectively; p = 0.24). In multivariate analysis, both female sex (OR: 2.992; CI: 1.22–7.34) and induction phase of treatment (OR: 3.953; CI: 1.085–14.403) were predictive of a favorable response. At a median follow-up of 5 months, 43 (35.2%) patients were dead; the 1-year overall survival (OS) was 49.9%. In multivariate analysis, the response to ISV (OR: 0.103; CI: 0.041–0.262) and IFD refractoriness to previous antifungals (OR: 3.413; CI: 1.318–8.838) were statistically significant for OS. Adverse events (AEs) were reported in 15/122 patients (12.3%); grade 3–4 AEs were reported in 5 (4%) and led to ISV discontinuation. Our study confirms the safety and tolerability of ISV, also in diseases other than acute leukemia. Phase of hematological disease, gender and refractoriness to previous antifungals are the main predictive factors for the aforementioned response and outcome.
Effect of Remnant Tissues on Outcomes of Anterior Cruciate Ligament Reconstruction at Follow-up Arthroscopy
Authors: Sueyoshi Ted , Nakatani Takuya
Published: December 2019

Background:

Remnant-preserving anterior cruciate ligament reconstruction (ACLR) is sought to enhance vascularization and maturation of a graft and to produce positive clinical outcomes after reconstruction.

Objective:

The purpose of this study was to investigate an effect of remnant anterior cruciate ligament (ACL) tissues on outcomes of ACLR 1 year after reconstruction in younger populations.

Design:

Retrospective chart review.

Setting:

Inpatient orthopedic surgical and rehabilitation clinic.

Subjects:

The subjects were 644 patients who underwent primary ACLR.

Independent Variables:

The independent variables were age, height, and body weight of the subjects, and the presence of remnant tissue.

Main Outcome Measures:

The outcome measure was the number of subjects with secondary infra-articular injuries at a follow-up arthroscopy after ACLR. The odds ratio was calculated and compared between the remnant-preserving ACLR (ACLR-P) and remnant-resecting (ACLR-R) groups to investigate the effect of remnant tissues on postoperative outcomes.

Results:

A total of 416 cases met our inclusion criteria and were included in this study. There were 136 cases (49 males and 87 females) in the ACLR-P group with the mean age (±SD) of 17.86 ± 2.85 years. There were 280 cases (106 males and 174 females) in the ACLR-R group, and the mean age (±SD) was 18.13 ± 2.73 years. Of 136 cases in the ALCR-P group, 54 (39.7%) had abnormal arthroscopic findings that lead to a surgical intervention. Of 280 patients in the ACLR-R group, 128 (45.7%) had abnormal findings. Odds ratio was 0.78 [95% confidence interval (CI), 0.51-1.18; P = 0.24]. Four cases in the ACLR-P group and 8 in the ACLR-R group were diagnosed with ACL retear during follow-up arthroscopy. Odds ratio was 1.03 (95% CI, 0.30-3.48; P = 0.96).

Conclusions:

The presence of ACL remnant tissues did not have a significant effect on outcomes 1 year after reconstruction. However, there was a trend that lower percentage of patients with remnant-preserving ALCR had abnormal arthroscopic findings that lead to a surgical treatment at follow-up arthroscopy 1 year after initial reconstruction. The presence of remnant tissues did not have a significant effect on retear rate.
How Computational Modeling can Help to Predict Gas Transfer in Artificial Lungs Early in the Design Process
Authors: Kaesler Andreas , Rosen Marius , Schlanstein Peter C , Wagner Georg , Groß-Hardt Sascha , Schmitz-Rode Thomas , Steinseifer Ulrich , Arens Jutta
Published: December 2019

Wearable extracorporeal membrane oxygenation (ECMO) circuits may soon become a viable alternative to conventional ECMO treatment. Common device-induced complications, however, such as blood trauma and oxygenator thrombosis, must first be addressed to improve long-term reliability, since ambulatory patients cannot be monitored as closely as intensive care patients. Additionally, an efficient use of the membrane surface can reduce the size of the devices, priming volume, and weight to achieve portability. Both challenges are linked to the hemodynamics in the fiber bundle. While experimental test methods can often only provide global and time-averaged information, computational fluid dynamics (CFD) can give insight into local flow dynamics and gas transfer before building the first laboratory prototype. In this study, we applied our previously introduced micro-scale CFD model to the full fiber bundle of a small oxygenator for gas transfer prediction. Three randomized geometries as well as a staggered and in-line configuration were modeled and simulated with Ansys CFX. Three small laboratory oxygenator prototypes were built by stacking fiber segments unidirectionally with spacers between consecutive segments. The devices were tested in vitro for gas transfer with porcine blood in accordance with ISO 7199. The error of the predicted averaged CFD oxygen saturations of the random 1, 2, and 3 configurations relative to the averaged in-vitro data (over all samples and devices) was 2.4%, 4.6%, 3.1%, and 3.0% for blood flow rates of 100, 200, 300, and 400 ml/min, respectively. While our micro-scale CFD model was successfully applied to a small oxygenator with unidirectional fibers, the application to clinically relevant oxygenators will remain challenging due to the complex flow distribution in the fiber bundle and high computational costs. However, we will outline our future research priorities and discuss how an extended mass transfer correlation model implemented into CFD might enable an a priori prediction of gas transfer in full size oxygenators.
What is the evidence for fluticasone exhalation delivery system in chronic rhinosinusitis?
Authors: Kovacs Alexander J. , Goshtasbi Khodayar , Kuan Edward C.
Published: December 2019

Purpose for review

The aim of this article is to review the current literature regarding a novel method of topically delivering nasal steroids, namely exhalation delivery system-fluticasone (EDS-FLU), for the treatment of chronic rhinosinusitis (CRS).

Recent findings

Recent Food and Drug Administration approval of EDS-FLU and increasing evidence surrounding its efficacy and safety has led to an additional tool for the treatment of chronic rhinosinusitis. Compared with placebo, EDS-FLU has demonstrated significant improvements in patients’ sinonasal symptoms and overall inflammatory control as well as quality of life measures. Additionally, using EDS-FLU can lead to polyp grade improvement and polyp elimination in patients with chronic rhinosinusitis with polyps. Furthermore, compared with controls, patients who received EDS-FLU were less likely to meet predefined surgical criteria at the conclusion of the study.

EDS-FLU has demonstrated significant improvement in managing symptoms and polyps in CRS. Receiving EDS-FLU was associated with a significant reduction in the proportion of patients meeting surgical criteria. Further studies are warranted to evaluate the long-term outcomes of EDS-FLU, especially as compared with steroid sprays and topical steroid irrigations, in management of CRS.
Latest developments on topical therapies in chronic rhinosinusitis
Authors: Tan Neil C.W. , Psaltis Alkis J.
Published: December 2019

Purpose of review

Topical therapies play an important role in the management of chronic rhinosinusitis (CRS). A detailed literature review was undertaken to appraise recent evidence surrounding current topical therapies and novel treatments used in the setting of recalcitrant CRS.

Recent findings

Effective sinus surgery aids in the delivery of topical therapies. Budesonide nasal rinses delivered by saline irrigation offer clinical and symptomatic improvements pre and postoperatively with a well-proven safety profile. Topical steroids may additionally offer direct antibacterial effects as per in-vitro testing. Topical antibiotics are not recommended in routine practice; however, they may be of benefit for short-term eradication therapy. Novel treatments are under keen investigation and include bacteriophage, colloidal silver and manuka honey. The evidence base for these treatments is not robust enough to recommend their routine use at present.

Topical steroids delivered in conjunction with saline nasal irrigation offer the best combination of treatments in CRS and should be considered a standard of care. Wide surgical access and aggressive surgical debridement of polyposis facilitates the delivery of steroid irrigations to sinonasal mucosa and is associated with improved long-term outcomes following endoscopic sinus surgery. The use of novel treatments remains within the research setting alone.
Chronic rhinosinusitis and sleep quality
Authors: Papagiannopoulos Peter , Kuan Edward C. , Tajudeen Bobby A.
Published: December 2019

Purpose of review

To review the recent literature describing the association between chronic rhinosinusitis and its effects on sleep quality.

Recent findings

Chronic rhinosinusitis (CRS) causes significantly worse sleep by both subjective and objective measures. CRS is also strongly associated with obstructive sleep apnea. Treating CRS surgically improves subjective sleep scores.

CRS worsens sleep quality both subjectively and objectively. Sleep quality is improved after endoscopic sinus surgery.
Imagining an Orientation Built on Trust
Authors: Beamer Jenna C. , Kromer Rachel S. , Jeffery Alvin D.
Published: December 2019

To streamline competency assessment documentation during orientation, we developed a comprehensive, three-phase plan, consisting of a tiered skills acquisition model, entrustable professional activities, and the full incorporation of Donna Wright’s recommendations for initial competency development, allowing for the transition away from the traditional skills checklist (Wright, 2005). We were able to reduce orientation time and preceptor confusion while increasing orientation process satisfaction by the end of our revisions.
Case Report of an Autopsy of a Child Who Died in a Drum-Type Washing Machine Tub
Authors: Tani Naoto , Ikeda Tomoya , Shida Alissa , Aoki Yayoi , Ikeda Kei , Morioka Fumiya , Ishikawa Takaki
Published: December 2019

The patient was a 5-year-old boy who was found in a state of cardiorespiratory arrest in the tub of a washing machine without water with the door closed. The autopsy findings included severe facial congestion and petechiae of the facial skin and palpebral conjunctiva. Several organs exhibited congestion. Hemorrhagic spots were seen on the serous membranes of various organs, with particularly marked hemorrhagic spots seen on the lungs. The heart contained fluid blood without soft clots. There were no findings indicative of marked trauma, intoxication, or hyperthermia. The examination results suggested that asphyxia had occurred in this case. However, there were no findings indicative of cervical compression, oronasal obstruction, or the presence of a foreign body in the respiratory tract. Image analysis showed the child could make postural changes inside the washing machine tub. Consequently, impaired thoracic movement and postural asphyxia were considered unlikely to have occurred. The results of blood gas analysis showed no evidence of marked hypercapnia. We, therefore, concluded that the cause of the child's death was asphyxia due to hypoxia caused by being in a closed space, that is, a washing machine tub.
Kawasaki Disease in a 3-Month-Old Infant
Authors: Nguyen Thanh , M'Buila Celestin , Bui van Tung , Barat Maxime , Loire Mathilde
Published: December 2019

Background

Kawasaki disease is an acute vasculitis occurring between 6 months and 5 years old. Patients younger than 6 months have mostly incomplete form. This clinical symptoms lead to confusion and delayed diagnosis.

Case Report

We developed the diagnostic difficulties with a 3-month-old infant. At the beginning, his incomplete presentation misled pediatricians.

Conclusions

We highlight the possibilities of Kawasaki disease in infants younger than 6 months. Indeed, every diagnostic delay increases cardiovascular risk. Nonetheless, in our case, treatment was prescribed in the first 5 days, and the patient developed aneurysms.
The chitin attenuator: Cross-talk between calcineurin and the cell wall salvage pathways prevents chitin overexpression and loss of fungal viability
Authors: Dantas Alessandra da Silva , Walker Louise A. , Gow Neil A.R.
Published: December 2019

Chitin is an essential structural polysaccharide component of the cell walls of fungi. Because chitin is not found in human cells it also represents an attractive target for antifungal therapy. Recent reports have suggested that Candida cells can resist killing by the antifungal echinocandin both in vitro and in vivo by up-regulating chitin synthesis and thereby sustaining cell wall integrity (Lee et al., 2012). However, when echinocandins are removed, the chitin content quickly returns to basal levels, suggesting that elevated chitin cell wall content represents a fitness cost. We show here that those cells that die in the presence of echinocandins often have supra-high rather than high chitin levels, and therefore having too much chitin in the cell wall may be detrimental for viability. Furthermore, mutants in the Ca2+/calcineurin pathway are associated with appearance of viable super-high chitin cells following cell wall stress, suggesting suggest that this pathway may negatively regulate other chitin stimulation pathways. We, therefore, propose that C. albicans has evolved a mechanism to maintain their chitin content high enough to protect cells against cell wall damage, but not so high that will negatively affect cell viability. In our model, the Ca2+/calcineurin pathway acts as a buffering system or attenuator in maintaining viable high chitin cells by coordinating both chitin upregulation and modulation of the cell wall integrity pathway, through negative regulation of the MAPK Mkc1 pathway. In summary, we have uncovered a novel mechanism used by C. albicans to survive cell wall stress imposed by echinocandin treatment.
Fungal Transformers: Tracking a Moving Target
Authors: Childers Delma , Avelar Gabriela Mol , Bain Judith , Pradhan Arnab , Larcombe Daniel , Erwig Lars , Gow Neil , Brown Alistair
Published: December 2019

In human hosts, the opportunistic fungal pathogen Candida albicans primarily proliferates in nutrient diverse niches. Environmental condition sensing regulates several fungal cellular features including, but not limited to, metabolism, cell wall elasticity, and virulence. In addition, yeast cell division exposes pathogen-associated molecular patterns (PAMPs) at the cell surface that are known to be immune-stimulatory (e.g. β-glucan). While various host environmental signals and cell wall stressors have been implicated in PAMP exposure in vitro, little is known about the molecular mechanisms that modulate PAMP exposure. We have shown that lactate, an alternative carbon source present in mucosal niches and produced by activated innate immune cells, acts as a signalling molecule to reduce β-glucan exposure. However, it is unknown whether the reduction in β-glucan exposure is the result of PAMP camouflaging by other cell wall components, PAMP modification, or a combination of both processes. We characterized the downstream effectors affecting PAMP exposure in response to different carbon sources and environmental conditions that C. albicans encounters during transit through host niches. Using proteomics, gene deletion analysis, and pharmacological assays, we identified the downstream effectors involved in evading β-glucan recognition by the host pattern recognition receptor, Dectin-1. We can also show microscopic changes to the overall distribution of Dectin-1-recognised β-glucan on the cell surface in response to masking conditions as well as alterations to the interactions of masked cells with phagocytes. Finally, we are examining the impact of PAMP modulation and its inhibition on disease outcomes.
Evaluating the use of variation graphs for the characterisation of yeast rDNA arrays
Authors: Ursani Ziauddin , Davey Robert , Dicks Jo
Published: December 2019

Over the past decade, we have gained considerable insight into the identification of sequence variation within the rDNA array of Saccharomyces cerevisiae and its closest wild relative, Saccharomyces paradoxus. Yet considerable challenges remain in the computational characterisation of this complex genomic region. This study aimed to evaluate the use of variation graphs for this purpose, formally comparing their effectiveness with traditional linear approaches.

Specifically, we aimed to identify both partial and fixed variants (i.e. pSNPs, SNPs, pINDELs and INDELs) in the rDNA arrays of 10 diverse, haploid Saccharomyces cerevisiae strains with high quality genomic datasets. We constructed two computational pipelines using two highly different approaches. The first pipeline used the BWA read mapper and the BCFtools variant caller to identify variants against the linear S288c reference, with the second pipeline using the vg tool to call variants against a graphical reference (either based on a graphical representation of the S288c genome or a Saccharomyces cerevisiae pan-genome).

The results showed that the graph-based pipeline was able to identify more variants than the linear pipeline, and in particular partial variants, while also missing some key variants identified by BWA/BCFtools. A major discrepancy between the two pipelines was found in the read coverage at loci where the vg pipeline identified variants. In the coming months, we aim to investigate the cause of these differences and to develop a new graph-based computational pipeline that can accurately identify the full range of sequence and copy number variation within this key genomic region.
Modification of Candida albicans cell wall by commensal gut bacteria
Authors: Buzun Ekaterina , Quinn Janet , Lowe Elisabeth
Published: December 2019

The human gut is populated with a vast community of microbes, the microbiota. Fungi comprise 0.1% of the total gut microbiota. Some of these fungi exist as benign members, however others such Candida albicans can undergo a pathogenic switch causing disease. The fungal cell wall is the first target for immune system recognition. Recent studies have suggested that Candida is decorated with different cell wall epitopes within different physiological niches, due to the impact of carbon source and oxygen availability on cell wall remodelling. Here we hypothesize that resident gut bacteria also play a major role in fungal cell wall remodelling and immune recognition. Data from our lab has shown that a common bacterium from the gut, Bacteroides thetaiotaomicron (Bt), produces an extensive repertoire of degradative enzymes to breakdown the Candida cell wall. Recently, we have identified novel enzymes in Bt from the glycoside hydrolase family 130 (GH130), which specifically target β1,2-linked mannan, a unique feature of Candida mannan. We have deleted multiple fungal mannan specific loci in Bt and examined the ability of deletion strains to utilise Candida mannan as a carbon source. These data suggest that Bt contains multiple pathways to degrade the Candida cell wall. Now we are systematically dissecting the impact of mannan degradation on the physiology of the fungus. This will provide insights into how two prominent members of the gut microbiota interact with each other, how the Candida cell wall is modified in the anaerobic environment of the gut, and the importance of this in promoting immune homeostasis.
Reincubation of culture-negative urines for an additional 20 hours does not identify additional UTI cases
Authors: Kocer Kaan , Zimmermann Stefan , Burckhardt Irene
Published: December 2019

Introduction. The question of whether a single day of incubation is sufficient for urine cultures has been a matter of debate.

Aim. The aim of this study was to investigate the potential benefit of prolonged incubation for initially culture-negative urines.

Methodology. Eight hundred and twelve urine specimens with no growth after incubation for 20 h were incubated for an additional 20 h to detect slower growing uropathogenic organisms.

Results. This study included a considerable number of urine cultures from immunocompromised and/or kidney-transplanted patients. For 99.9 % of the specimens, there was no difference in the interpretation of results.

Conclusion. Twenty hours of incubation did not have any negative effect on the detection of uropathogens.
Structure and function of the bacterial protein toxin phenomycin
Authors: Hansen Bente K. , Larsen Camilla K. , Nielsen Jacob T. , Svenningsen Esben B. , Van Lan B. , Jacobsen Kristian M. , Bjerring Morten , Flygaard Rasmus K. , Jenner Lasse B. , Nejsum Lene N. , Brodersen Ditlev E. , Mulder Frans A. A. , Tørring Thomas , Poulsen Thomas B.
Published: December 2019

Phenomycin is a bacterial mini-protein of 89 amino acids discovered more than 50 years ago with toxicity in the nanomolar regime towards mammalian cells. The protein inhibits the function of the eukaryotic ribosome in cell free systems and appears to target translation initiation. Several fundamental questions concerning the cellular activity of phenomycin have however remained unanswered. In this paper, we have used morphological profiling to show that direct inhibition of translation underlies the toxicity of phenomycin in cells. We have performed studies of the cellular uptake mechanism of phenomycin, showing that endosomal escape is the toxicity-limiting step, and we have solved a solution phase high-resolution structure of the protein using NMR spectroscopy. Through bioinformatic as well as functional comparisons between phenomycin and two homologs, we have identified a peptide segment, which constitutes one of two loops in the structure, that is critical for the toxicity of phenomycin.
Intensive infection control responses and whole genome sequencing to interrupt and resolve widespread transmission of OXA-181 Escherichia coli in a hospital setting
Authors: Roberts Leah W. , Forde Brian M. , Henderson Andrew , Playford E. Geoffrey , Runnegar Naomi , Henderson Belinda , Watson Catherine , Lindsay Margaret , Bursle Evan , Douglas Joel , Paterson David L. , Schembri Mark A , Harris Patrick N.A. , Beatson Scott A.
Published: December 2019

Background

OXA-48-like carbapenemases have become increasingly prevalent in healthcare settings worldwide. Their low-level activity against carbapenems makes them difficult to identify, causing problems for infection control. Here we present an outbreak of Escherichia coli producing OXA-181 (part of the OXA-48 family of carbapenemases) in a Queensland Hospital, and describe how we used whole genome sequencing (WGS) to identify the outbreak strain, determine the extent of transmission within the hospital and support infection control responses.

Methods

116 isolates were collected and sequenced on an Illumina NextSeq to determine species, sequence type (ST) and presence of resistance genes. Core single nucleotide polymorphisms were used to determine strain relatedness. Three isolates were also sequenced on an Oxford Nanopore MinION to determine the context of the resistance genes.

Results

Of 116 isolates, 85 (84 E. coli and one K. pneumoniae) from 78 patients (and two environmental sources) were related to the ongoing outbreak. The outbreak E. coli strain was found to be ST38 and carried blaOXA-181, blaCTX-M-15 and qnrS1 genes. Long read sequencing revealed blaOXA-181 to be carried on an IncX3 plasmid with qnrS1. blaCTX-M-15 was chromosomally integrated (via ISEcp1 insertion) in close proximity to a second qnrS1 gene. A search of the laboratory database identified an isolate with an identical unusual antibiogram from a patient recently admitted to a hospital in Vietnam, suggesting that the strain was introduced to the hospital. This conclusion was supported by WGS, as comparison of the strain to public data identified a close match to an E. coli recovered from Vietnam in 2011.

Conclusion

A blaOXA-181-carrying E. coli ST38 strain was introduced to a Brisbane hospital and spread undetected throughout multiple wards over several months. Using WGS, we characterized the outbreak strain and unambiguously detected its presence throughout the hospital. We show how both WGS and infection control measures can be utilized to effectively terminate widespread transmission of an elusory pathogen.
Convergent evolution of seasonal camouflage in response to reduced snow cover across the snowshoe hare range
Authors: Jones Matthew R. , Mills L. Scott , Jensen Jeffrey D. , Good Jeffrey M.
Published: December 2019

Determining how different populations adapt to similar environments is fundamental to understanding the limits of adaptation under changing environments. Snowshoe hares (Lepus americanus) typically molt into white winter coats to remain camouflaged against snow. In some warmer climates, hares have evolved brown winter camouflage – an adaptation that may spread under climate change. We used extensive range-wide genomic data to 1) resolve broad-scale patterns of population structure and gene flow and 2) investigate the factors shaping the origins and distribution of winter-brown camouflage variation. In coastal Pacific Northwest (PNW) populations, winter-brown camouflage is known to be determined by a recessive haplotype at theAgoutipigmentation gene. Our phylogeographic analyses revealed deep structure and limited gene flow between PNW and more northern Boreal populations, where winter-brown camouflage is rare along the range edge. Genome sequencing of a winter-brown snowshoe hare from Alaska shows that it lacks the winter-brown PNW haplotype, reflecting a history of convergent phenotypic evolution. However, the PNW haplotype does occur at low frequency in a winter-white population from Montana, consistent with the spread of a locally deleterious recessive variant that is masked from selection when rare. Simulations show that if annual snow cover dramatically declined in the same population, then the predicted selective increase in frequency of the now beneficial winter-brownAgoutiallele is likely to be extremely slow due to the same masking effect. Our findings underscore how allelic dominance can shape the geographic extent and rate of convergent adaptation in response to rapidly changing environments.
Dual-task Interference in a Simulated Driving Environment: Serial or Parallel Processing?
Authors: Abbas-Zadeh Mojtaba , Hossein-Zadeh Gholam-Ali , Vaziri-Pashkam Maryam
Published: December 2019

When humans are required to perform two tasks concurrently, their performances decrease as the two tasks get closer together in time. This effect is known as dual-task interference. This limitation of the human brain could have lethal effects during demanding everyday tasks such as driving. Are the two tasks processed serially or in parallel during dual-task performance in naturalistic settings? Here, we investigated dual-task interference in a simulated driving environment and investigated the serial/parallel nature of processing during dual-task performance. Participants performed a lane change task on a desktop computer, along with an image discrimination task. We systematically varied the time difference between the onset of the two tasks (Stimulus Onset Asynchrony, SOA) and measured its effect on the amount of dual-task interference. Results showed that the reaction times (RTs) of two tasks in the dual-task condition were higher than those in the single-task condition. SOA influenced RTs of both tasks when they were presented second and the RTs of the image task when it was presented first. Manipulating the predictability of the order of the two tasks, we showed that unpredictability attenuated the effect of SOA by changing the order of the response to the two tasks. Next, using drift-diffusion modeling, we modeled the reaction time and choice of the subjects during dual-task performance in both predictable and unpredictable task order conditions. The modeling results indicated that performing two tasks concurrently, affects both the rate of evidence accumulation and the delays outside the evidence accumulation period, suggesting that the two tasks are performed in a partial-parallel manner. These results extend the findings of previous dual-task experiments to more naturalistic settings and deepen our understanding of the mechanisms of dual-task interference.
Similar levels of emotional contagion in male and female rats
Authors: Han Yingying , Sichterman Bo , Carrillo Maria , Gazzola Valeria , Keysers Christian
Published: December 2019

Emotional contagion, the ability to feel what other individuals feel, is thought to be an important element of social life. In humans, emotional contagion has been shown to be stronger in women than men. Emotional contagion has been shown to exist also in rodents, and a growing number of studies explore the neural basis of emotional contagion in male rats and mice. These studies promise to shed light on the mechanisms that might go astray in psychiatric disorders characterized by dysfunctions of emotional contagion and empathy. Here we explore whether there are sex differences in emotional contagion in rats. We use an established paradigm in which a demonstrator rat receives footshocks while freezing is measured in both the demonstrator and an observer rat, which can hear, smell and see each other. By comparing pairs of male rats with pairs of female rats, we find (i) that female demonstrators freeze less when submitted to footshocks, but that (ii) the emotional contagion response, i.e. the degree of influence across the rats, does not depend on the sex of the rats. This was true whether emotional contagion was quantified based on the slope of a regression linking demonstrator and observer average freezing, or on Granger causality estimates of moment-to-moment freezing. The lack of sex differences in emotional contagion is compatible with an interpretation of emotional contagion as serving selfish danger detection.
Spontaneous generation of face recognition in untrained deep neural networks
Authors: Baek Seungdae , Song Min , Jang Jaeson , Kim Gwangsu , Paik Se-Bum
Published: December 2019

Face-selective neurons are observed in the primate visual pathway and are considered the basis of facial recognition in the brain. However, it is debated whether this neuronal selectivity can arise spontaneously, or requires training from visual experience. Here, we show that face-selective neurons arise spontaneously in random feedforward networks in the absence of learning. Using biologically inspired deep neural networks, we found that face-selective neurons arise under three different network conditions: one trained using non-face natural images, one randomized after being trained, and one never trained. We confirmed that spontaneously emerged face-selective neurons show the biological view-point-invariant characteristics observed in monkeys. Such neurons suddenly vanished when feedforward weight variation declined to a certain level. Our results suggest that innate face-selectivity originates from statistical variation of the feedforward projections in hierarchical neural networks.
Interactions between the neural correlates of dispositional internally directed thought and visual imagery
Authors: Karapanagiotidis Theodoros , Jefferies Elizabeth , Smallwood Jonathan
Published: December 2019

Cognition is not always directed to the events in the here and now and we often self-generate thoughts and images in imagination. Important aspects of these self-generated experiences are associated with various dispositional traits. In this study, we explored whether these psychological associations relate to a common underlying neurocognitive mechanism. We acquired resting state functional magnetic resonance imaging data from a large cohort of participants and asked them to retrospectively report their experience during the scan. Participants also completed questionnaires reflecting a range of dispositional traits. We found thoughts emphasising visual imagery at rest were associated with dispositional tendency towards internally directed attention (self-consciousness and attentional problems) and linked to a stronger correlation between a posterior parietal network and a lateral fronto-temporal network. Furthermore, decoupling between the brainstem and a lateral visual network was associated with dispositional internally directed attention. Critically, these brain-cognition associations were related: the correlation between parietal-frontal regions and reports of visual imagery was stronger for individuals with increased connectivity between brainstem and visual cortex. Our results highlight neural mechanisms linked to the dispositional basis for patterns of self-generated thought, and suggest that accounting for dispositional traits is important when exploring the neural substrates of self-generated experience (and vice versa).
Glycan-dependent two-step cell adhesion mechanism of Tc toxins
Authors: Roderer Daniel , Bröcker Felix , Sitsel Oleg , Kaplonek Paulina , Leidreiter Franziska , Seeberger Peter H. , Raunser Stefan
Published: December 2019

Toxin complex (Tc) toxins are virulence factors widespread in insect and human bacterial pathogens. Tcs are composed of three subunits: TcA, TcB and TcC. TcA facilitates receptor-toxin interaction and membrane permeation, TcB and TcC form a toxin-encapsulating cocoon. While the mechanisms of holotoxin assembly and prepore-to-pore transition have been well-described, little is known about receptor binding and cellular uptake of Tcs. Here, we identify two classes of glycans, heparins/heparan sulfates and Lewis antigens, that act as receptors for different TcAs from insect- and human pathogenic bacteria. Glycan array screening and electron cryo microscopy (cryo-EM) structures reveal that all tested TcAs bind unexpectedly with their α-helical part of the shell domain to negatively charged heparins. In addition, TcdA1 from the insect-pathogen Photorhabdus luminescens binds to Lewis antigens with micromolar affinity. A cryo-EM structure of the TcdA1-Lewis X complex reveals that the glycan interacts with the receptor-binding domain D of the toxin. Our results suggest a two-step association mechanism of Tc toxins involving glycans on the surface of host cells.