bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical Features of Hemodialysis (HD) patients confirmed with Coronavirus Disease 2019 (COVID-19): a Retrospective Case-Control Study
Authors: Zhou Huan , Xiao Xiaofen , Wang Xiaohui , Tan Xianhua , Zhang Xin , He Yong , Li Jing , Yang Guosheng , Li Mingmei , Liu Duan , Han Shanshan , Kuang Haibo
Published: July 2020

Background

Since December 2019, Coronavirus Disease 2019(COVID-19) occurred in wuhan, China, and outbreaked rapidly into a global pandemic. This current poses great challenges to hemodialysis (HD) patients.

Objective

To make a comprehensive evaluation and comparison between HD patients confirmed with COVID-19 and the general HD patients.

Methods

HD patients confirmed with COVID-19 in Wuhan No.5 Hospital were admitted as confirmed group from Jan 10 to Mar 15, 2020. And HD patients not infected in our dialysis center were chosen as control group. General characteristics, laboratory indicators were retrospectively collected, analyzed and compared.

Results

A total of 142 cases were admitted, including 43 cases in confirmed group and 99 in control group. Body mass index (BMI) was slightly lower in confirmed group than that in control group (P=0.011). The proportion of one or less underlying disease in confirmed group(51.16%) was higher than that in control group(14.14%)(P< 0.001), and the proportion of three or more underlying diseases in confirmed group(11.63%) was lower than that in control group(52.53%)(P< 0.001). Patients in confirmed group exhibited significantly lower hemoglobin, lymphocyte count, and lymphocyte percentage, but higher neutrophil percentage, neutrophil-to-lymphocyte ratio (NLR), C-reactive protein, aspartate transaminase, and alkaline phosphatase. There was no significant difference in age, gender, dialysis age, primary disease, the using of ACEI/ARB, platelet-to-lymphocyte ratio (PLR), and other indicators between the two groups.

Conclusions

Faced with Severe Acute Respiratory Syndrome-CoV-2 (SARS-CoV-2), HD patients with lower BMI and hemoglobin were more susceptible to be infected, which might be related to malnutrition. Once confirmed with COVID-19, HD patients expressed obviously dis-regulated of inflammation and immune.
Targeted molecular profiling of rare cell populations identifies olfactory sensory neuron fate and wiring determinants
Authors: Arguello J. Roman , Abuin Liliane , Armida Jan , Mika Kaan , Chai Phing Chian , Benton Richard
Published: July 2020

Determining the molecular properties of neurons is essential to understand their development, function and evolution. We used Targeted DamID (TaDa) to characterize RNA polymerase II occupancy and chromatin accessibility in selected Ionotropic Receptor (IR)-expressing sensory neurons in theDrosophilaantenna. Although individual populations represent a minute fraction of cells, TaDa is sufficiently sensitive and specific to identify the expected receptor genes. UniqueIrexpression is not linked to substantial differences in chromatin accessibility, but rather to distinct transcription factor profiles. Heterogeneously-expressed genes across populations are enriched for neurodevelopmental factors, and we identify functions for the POU-domain protein Pdm3 as a genetic switch of Ir neuron fate, and the atypical cadherin Flamingo in segregation of neurons into discrete glomeruli. Together this study reveals the effectiveness of TaDa in profiling rare neural populations, identifies new roles for a transcription factor and a neuronal guidance molecule, and provides valuable datasets for future exploration.
Increased SGK1 activity potentiates mineralocorticoid/NaCl-induced hypertension and kidney injury
Authors: Sierra-Ramos Catalina , Velazquez-Garcia Silvia , Keskus Ayse G. , Vastola-Mascolo Arianna , Rodríguez-Rodríguez Ana E. , Luis-Lima Sergio , Hernández Guadalberto , Navarro-González Juan F. , Porrini Esteban , Konu Ozlen , de la Rosa Diego Alvarez
Published: July 2020

The serum and glucocorticoid-induced kinase 1 (SGK1) stimulates aldosterone-dependent renal Na+ reabsorption and modulates blood pressure. In addition, genetic ablation or pharmacological inhibition of SGK1 limits the development of kidney inflammation and fibrosis in response to excess mineralocorticoid signalling. In this work we tested the hypothesis that a systemic increase in SGK1 activity would potentiate mineralocorticoid/salt-induced hypertension and kidney injury. To that end, we used a transgenic mouse model with increased SGK1 activity. Mineralocorticoid/salt-induced hypertension and kidney damage was induced by unilateral nephrectomy and treatment with deoxycorticosterone acetate and NaCl in drinking water for six weeks. Our results demonstrate higher systolic blood pressure in treated transgenic mice when compared to wild type counterparts. Transgenic mice showed a mild increase in glomerular filtration rate, increased albuminuria, exacerbated glomerular hypertrophy and fibrosis. Transcriptomic analysis showed that extracellular matrix and immune response related terms were enriched in the downregulated and upregulated genes, respectively, in transgenic mice. In conclusion, we propose that systemically increased SGK1 activity is a risk factor for the development of mineralocorticoid-dependent hypertension and incipient kidney injury in the context of low renal mass.
Alpha/beta power decreases during episodic memory formation predict the magnitude of alpha/beta power decreases during subsequent retrieval
Authors: Griffiths Benjamin J. , Martín-Buro María Carmen , Staresina Bernhard P. , Hanslmayr Simon , Staudigl Tobias
Published: July 2020

Episodic memory retrieval is characterised by the vivid reinstatement of information about a personally-experienced event. Growing evidence suggests that the reinstatement of such information is supported by reductions in the spectral power of alpha/beta activity. Given that the amount of information that can be recalled depends on the amount of information that was originally encoded, information-based accounts of alpha/beta activity would suggest that retrieval-related alpha/beta power decreases similarly depend upon decreases in alpha/beta power during encoding. To test this hypothesis, seventeen human participants completed a sequence-learning task while undergoing concurrent MEG recordings. Regression-based analyses were then used to estimate how alpha/beta power decreases during encoding predicted alpha/beta power decreases during retrieval, on a trial-by-trial basis. When subjecting these parameter estimates to group-level analysis, we find evidence to suggest that retrieval-related alpha/beta (7-15Hz) power decreases fluctuate as a function of encoding-related alpha/beta power decreases. These results suggest that retrieval-related alpha/beta power decreases are contingent on the decrease in alpha/beta power that arose during encoding. Subsequent analysis uncovered no evidence to suggest that these alpha/beta power decreases reflect stimulus identity, indicating that the contingency between encoding- and retrieval-related alpha/beta power reflects the reinstatement of a neurophysiological operation, rather than neural representation, during episodic memory retrieval.
The RNA helicase DDX5 promotes alveolar rhabdomyosarcoma growth and survival
Authors: Gualtieri Alberto , Licursi Valerio , Mozzetta Chiara
Published: July 2020

Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma of childhood characterized by the inability to exit the proliferative myoblast-like stage. The alveolar fusion positive subtype (FP-ARMS) is the most aggressive and is mainly caused by the expression of PAX3/7-FOXO1 oncoproteins, which are challenging pharmacological targets. Thus, other therapeutic vulnerabilities resulting from gene expression changes are progressively being recognized. Here, we identified the DEAD box RNA helicase 5 (DDX5) as a potential therapeutic target to inhibit FP-ARMS growth. We show that DDX5 is overexpressed in alveolar RMS cells, demonstrating that its depletion drastically decreases FP-ARMS viability and slows tumor growth in xenograft models. Mechanistically, we provide evidence that DDX5 functions upstream the G9a/AKT survival signalling pathway, by modulating G9a protein stability. Finally, we show that G9a interacts with PAX3-FOXO1 and regulates its activity, thus sustaining FP-ARMS myoblastic state. Together, our findings identify a novel survival-promoting loop in FP-ARMS and highlight DDX5 as potential therapeutic target to arrest rhabdomyosarcoma growth.
Spatial odor discrimination in hawkmoth,Manduca sexta(L.)
Authors: Kalyanasundaram P. , Willis M. A.
Published: July 2020

Flying insects track turbulent odor plumes to find mates, food and egg-laying sites. To maintain contact with the plume, insects are thought to adapt their flight control according to the distribution of odor in the plume using the timing of odor onsets and intervals between odor encounters. Although timing cues are important, few studies have addressed whether insects are capable of deriving spatial information about odor distribution from bilateral comparisons between their antennae in flight. The proboscis extension reflex (PER) associative learning protocol, originally developed to study odor learning in honeybees, was modified to show hawkmoths,Manduca sexta, can discriminate between odor stimuli arriving on either antenna. We show moths discriminated the odor arrival side with an accuracy of >70%. The information about spatial distribution of odor stimuli is thus available to moths searching for odor sources, opening the possibility that they use both spatial and temporal odor information.
A Saudi G6PD Deficient Girl Died with Pediatric Multisystem Inflammatory Syndrome-COVID-19
Authors: Al-Aamri Maryam A. , Al-Khars Fatimah T. , Alkhwaitem Sami J. , AlHassan Abdulaziz K. , Aithan Ali M. Al , Alkhalifa Fatima H. , Al-Abdi Sameer Y.
Published: July 2020

Reports on pediatric multisystem inflammatory syndrome (PMIS) temporally related to coronavirus disease 2019 (COVID-19) are increasing. African and Afro-Caribbean children constituted about 37% of the cases in these reports. Although glucose-6-phosphatase dehydrogenase (G6PD) deficiency is common among this population, the G6PD status of these cases has not been reported. We report the first case of PMIS related to COVID-19 from Saudi Arabia. This case was a Saudi G6PD deficient girl who died with PMIS related to COVID-19. G6PD deficiency induces redox imbalance and exaggerates the inflammatory response; thus, it might contribute to the development or the grave outcome of our case. We urgently need to assess the association between G6PD deficiency and COVID-19 in a large study as the G6PD deficiency may be a useful predictor for the progression of the COVID-19.
Designing the ASPIRE-SSI study: a multicenter, observational, prospective cohort study to assess the incidence and risk factors of surgical site and bloodstream infections caused by Staphylococcus aureus in Europe
Authors: Troeman Darren P.R. , Weber Susanne , Hazard Derek , Wolkewitz Martin , Timbermount Leen , Vilken Tuba , Harbarth Stephan , Ali Omar , Sifakis Frangiscos , Kluytmans Jan A.J.W.
Published: July 2020

Background

There is a continuing need for in-depth and updated knowledge about the epidemiology of surgical site infections (SSIs) caused by Staphylococcus aureus to support the development of effective preventive interventions. The ASPIRE-SSI study aims primarily to determine the incidence of S. aureus SSIs and postoperative bloodstream infections (BSIs) in Europe and to assess their association with patient-related, pathogen-related, and contextual risk factors.

Methods

ASPIRE-SSI is a prospective, multicenter, observational cohort study primarily assessing the incidence of and risk factors for S. aureus SSI and postoperative BSI in Europe. Five thousand adult surgical patients (of which two-thirds will be S. aureus carriers and one-third non-carriers) undergoing several types of surgical procedures in sites located across Europe were enrolled in the study. Data and specimens were collected from these subjects who were followed for up to 90 days following surgery to assess study outcomes.

Using advanced survival analyses and regression techniques (including competing risks models), we will determine event-specific and sub-distribution hazards to assess the independent associations of these study outcomes with risk factors. Additionally, a risk prediction model will be derived to quantify the risk of developing SSI or BSI due to S. aureus.

Discussion

Despite the challenges, this study will provide important and contemporary information about the epidemiology of SSI and BSI (and other infections) caused by S. aureus in the current surgical population in Europe, thereby supporting the development of effective preventive interventions.

Trial registration

clinicaltrial.gov number NCT02935244
A Multicenter, randomized, open-label, controlled trial to evaluate the efficacy and tolerability of hydroxychloroquine and a retrospective study in adult patients with mild to moderate Coronavirus disease 2019 (COVID-19)
Authors: Chen Cheng-Pin , Lin Yi-Chun , Chen Tsung-Chia , Tseng Ting-Yu , Wong Hon-Lai , Kuo Cheng-Yu , Lin Wu-Pu , Huang Sz-Rung , Wang Wei-Yao , Liao Jia-Hung , Liao Chung-Shin , Hung Yuan-Pin , Lin Tse-Hung , Chang Tz-Yan , Hsiao Chin-Fu , Huang Yi-Wen , Chung Wei-Sheng , Cheng Chien-Yu , Cheng Shu-Hsing
Published: July 2020

Objective

In this study, we evaluated the efficacy of hydroxychloroquine (HCQ) against coronavirus disease 2019 (COVID-19) via a randomized controlled trial (RCT) and a retrospective study.

Methods

Subjects admitted to 11 designated public hospitals in Taiwan between April 1 and May 31, 2020, with COVID-19 diagnosis confirmed by pharyngeal real-time RT-PCR for SARS-CoV-2, were randomized at a 2:1 ratio and stratified by mild or moderate illness. HCQ 400 mg twice for 1 d and HCQ 200 mg twice daily for 6 days were administered. Both study group and controlled group received standard of care (SOC). Pharyngeal swabs and sputum were collected every other day. The proportion and time to negative viral PCR were assessed on day 14. In the retrospective study, medical records were reviewed for patients admitted before March 31, 2020.

Results

There were 33 and 37 cases in the RCT and retrospective study, respctively. In the RCT, the median times to negative rRT-PCR from randomization to hospital day 14 were 5 days (95% CI; 1–9 days) and 10 days (95% CI; 2–12 days) for the HCQ and SOC groups, respectively (p = 0.40). On day 14, 81.0% (17/21) and 75.0% (9/12) of the subjects in the HCQ and SOC groups, respectively, had undetected virus (p = 0.36). In the retrospective study, 12 (42.9%) in the HCQ group and 5 (55.6%) in the control group had negative rRT-PCR results on hospital day 14 (p = 0.70).

Conclusions

Neither study demonstrated that HCQ shortened viral shedding in mild to moderate COVID-19 subjects.
Post-lockdown detection of SARS-CoV-2 RNA in the wastewater of Montpellier, France
Authors: Trottier Julie , Darques Regis , Mouheb Nassim Ait , Partiot Emma , Bakhache William , Deffieu Maika S. , Gaudin Raphael
Published: July 2020

The evolution of the COVID-19 pandemic can be monitored through the detection of SARS-CoV-2 RNA in sewage. Here, we measured the amount of SARS-CoV-2 RNA at the inflow point of the main waste water treatment plant (WWTP) of Montpellier, France. We collected samples 4 days before the end of lockdown and up to 45 days post-lockdown. We detected increased amounts of SARS-CoV-2 RNA at the WWTP, which was not correlated with the number of newly diagnosed patients. Future epidemiologic investigations may explain such asynchronous finding.
COVIDPEN: A Novel COVID-19 Detection Model using Chest X-Rays and CT Scans
Authors: Jaiswal Amit Kumar , Tiwari Prayag , Rathi Vipin Kumar , Qian Jia , Pandey Hari Mohan , Albuquerque Victor Hugo C.
Published: July 2020

The trending global pandemic of COVID-19 is the fastest ever impact which caused people worldwide by severe acute respiratory syndrome (SARS)-driven coronavirus. However, several countries suffer from the shortage of test kits and high false negative rate in PCR test. Enhancing the chest X-ray or CT detection rate becomes critical. The patient triage is of utmost importance and the use of machine learning can drive the diagnosis of chest X-ray or CT image by identifying COVID-19 cases. To tackle this problem, we propose COVIDPEN - a transfer learning approach on Pruned EfficientNet-based model for the detection of COVID-19 cases. The proposed model is further interpolated by post-hoc analysis for the explainability of the predictions. The effectiveness of our proposed model is demonstrated on two systematic datasets of chest radiographs and computed tomography scans. Experimental results with several baseline comparisons show that our method is on par and confers clinically explicable instances, which are meant for healthcare providers.
Topographic deep artificial neural networks reproduce the hallmarks of the primate inferior temporal cortex face processing network
Authors: Lee Hyodong , Margalit Eshed , Jozwik Kamila M. , Cohen Michael A. , Kanwisher Nancy , Yamins Daniel L. K. , DiCarlo James J.
Published: July 2020

A salient characteristic of monkey inferior temporal (IT) cortex is the IT face processing network. Its hallmarks include: “face neurons” that respond more to faces than non-face objects, strong spatial clustering of those neurons in foci at each IT anatomical level (“face patches”), and the preferential interconnection of those foci. While some deep artificial neural networks (ANNs) are good predictors of IT neuronal responses, including face neurons, they do not explain those face network hallmarks. Here we ask if they might be explained with a simple, metabolically motivated addition to current ANN ventral stream models. Specifically, we designed and successfully trained topographic deep ANNs (TDANNs) to solve real-world visual recognition tasks (as in prior work), but, in addition, we also optimized each network to minimize a proxy for neuronal wiring length within its IT layers. We report that after this dual optimization, the model IT layers of TDANNs reproduce the hallmarks of the IT face network: the presence of face neurons, clusters of face neurons that quantitatively match those found in IT face patches, connectivity between those patches, and the emergence of face viewpoint invariance along the network hierarchy. We find that these phenomena emerge for a range of naturalistic experience, but not for highly unnatural training. Taken together, these results show that the IT face processing network could be a consequence of a basic hierarchical anatomy along the ventral stream, selection pressure on the visual system to accomplish general object categorization, and selection pressure to minimize axonal wiring length.
Stimulation of Locus Coeruleus Noradrenergic System Modulates Sensory Processing and Brain State in two Different Time Scales
Authors: Fazlali Zeinab , Ranjbar-Slamloo Yadollah , Zabeh Erfan , Arabzadeh Ehsan
Published: July 2020

Locus Coeruleus (LC) noradrenergic system has widespread projections throughout the brain and affects sensory processing. LC modulation of sensory-evoked cortical activity and brain state is documented by electrical micro-stimulation, optogenetic experiments, and the local application of norepinephrine (NE). The temporal profile of the LC modulation of sensory response and brain state is not well characterized. Our goal in this study is to characterize this modulation. Here, we recorded neuronal activity from the barrel cortex (BC) of urethane-anesthetized rats while combining LC micro-stimulation with brief mechanical deflections of the whiskers at 10 different time lags (50-500 ms). We recorded spikes and local field potentials to quantify the neuronal activity and the brain state. LC micro-stimulation exhibited a biphasic effect on spontaneous activity of the BC: a period of suppression followed by a period of excitation. We observed a similar effect on the sensory-evoked response: at 50-ms lag, the evoked response decreased while at 150-ms lag, the early evoked response was facilitated. At 150 to 350-ms time lags, LC micro-stimulation caused a combined facilitation followed by suppression of the evoked response. In contrast to the fast transient effect of LC stimulation on BC spiking activity, brain state modulation started later and lasted longer. LC stimulation suppressed low-frequency activities that are associated with low arousal states. In summary, we found that LC modulation affects cortical processing of sensory inputs and the brain state at different time scales which are likely to involve distinct circuit mechanisms.
HIP1 mediates oncogenic transformation and cancer progression through STAT3 signalling
Authors: Bantval Rao Roheet , Ramos-Montoya Antonio , Scott Helen , Berry Lorraine , Reichelt Stefanie , MacArthur Stewart , Russell Roslin , Neal David E , Evergren Emma , Mills Ian G
Published: July 2020

Background

Huntingtin-interacting protein 1 (HIP1) is an adaptor protein involved in transcriptional regulation and receptor-mediated endocytosis. Overexpression of HIP1 transforms cell and is associated with, increasing grades of prostate cancer (CaP) and poor patient outcomes. However, the precise mechanism for the role of HIP1 in prostate cancer progression remains unknown.

Methods

Using a phospho-kinase antibody array we identified changes in signalling associated with HIP1 overexpression PNT1 cells. For validation Western blots were used together with knockdown or inhibitor treatments and phenotypic assays for cellular transformation. The cell line was xenografted to assess tumour growth. Gene expression microarray analysis of the cell line was used to identify perturbations in transcript levels.

Results

Here we demonstrate cellular transformation and phenotypic effects of HIP1 overexpression in a benign prostate epithelial cell line to be dependent on STAT3 signalling.In vivoxenografts confirmed the cellular transformation phenotype. Gene expression analysis revealed serum protein GDF15 to be a marker of prostate cancer tumorigenesis in our model. We present a HIP1-STAT3-GDF15 axis in our pre-clinical model that mediates cellular transformation and tumorigenesis.

Conclusion

Our findings provide a model defining the functional effects of increased HIP1 expression in prostate tumorigenesis and progression. This model implicates increased STAT3 signalling in HIP1-dependent prostate carcinogenesis and identifies GDF15 as a secreted factor supporting this process. The role of HIP1-STAT3-GDF15 signalling may extend to other epithelial cancers shown to overexpress HIP1; such as gliomas, colon and breast cancer where STAT3 is an emerging oncology drug target.
Enthalpy efficiency of the soleus muscle explains improvements in running economy
Authors: Bohm Sebastian , Mersmann Falk , Santuz Alessandro , Arampatzis Adamantios
Published: July 2020

During human running, the soleus, as the main plantar flexor muscle, generates the majority of the mechanical work through active shortening. The fraction of chemical energy that is converted into muscular work (i.e. the enthalpy efficiency) depends on the muscle shortening velocity. Here, we investigated the soleus muscle fascicle behavior during running with respect to the enthalpy efficiency as a mechanism that could explain previously reported improvements in running economy after exercise-induced increases of plantar flexor strength and Achilles tendon stiffness. Healthy amateur runners were randomly assigned to a control (n=10) or intervention group (n=13), which performed a specific 14-week muscle-tendon training. Significant increases in plantar flexor maximum strength (10%) and Achilles tendon stiffness (31%) yet reduced metabolic cost of running (4%) was found only in the intervention group (p<0.05). Following training, the soleus fascicle velocity profile throughout stance was altered, with the fascicles operating at a higher enthalpy efficiency during the phase of muscle-tendon unit lengthening (15%) and in average over stance (7%, p<0.05). These findings show that the improvements in energetic cost following increases in plantar flexor strength and Achilles tendon stiffness can be attributed to increased enthalpy efficiency of the operating soleus. This provides the first experimental evidence that the soleus enthalpy efficiency is a determinant of human running economy. Furthermore, the current results imply that the soleus energy production in the first part of the stance phase were the muscle-tendon unit is lengthening is crucial for the overall metabolic energy cost of running.
InteBac - An integrated bacterial and baculovirus expression vector suite
Authors: Altmannova Veronika , Blaha Andreas , Astrinidis Susanne , Reichle Heidi , Weir John R.
Published: July 2020

The successful production of recombinant protein for biochemical, biophysical and structural biological studies critically depends on the correct expression organism. Currently the most commonly used expression organisms for structural studies areE. coli(ca. 70% of all PDB structures) and the baculovirus/ insect cell expression system (ca. 5% of all PDB structures). While insect cell expression is frequently successful for large eukaryotic proteins, it is relatively expensive and time consuming compared toE. coliexpression. Frequently the decision to carry out a baculovirus project means restarting cloning from scratch. Here we describe an integrated system that allows the simultaneous cloning intoE. coliand baculovirus expression vectors using the same PCR products. The system offers a flexible array of N- and C-terminal affinity, solublisation and utility tags, and the speed allows expression screening to be completed inE. coli, before carrying out time and cost intensive experiments in baculovirus. Importantly, we describe a means of rapidly generating polycistronic bacterial constructs based on the hugely successful biGBac system, making InteBac of particular interest for researchers working on recombinant protein complexes.
Gut microbiota profiles of treatment-naïve adult acute myeloid leukemia patients with neutropenic fever during intensive chemotherapy
Authors: Rattanathammethee Thanawat , Tuitemwong Pimchanok , Thiennimitr Parameth , Sarichai Phinitphong , Pombejra Sarisa Na , Piriyakhuntorn Pokpong , Hantrakool Sasinee , Chai-Adisaksopha Chatree , Rattarittamrong Ekarat , Tantiworawit Adisak , Norasetthada Lalita
Published: July 2020

Intestinal bacterial flora of febrile neutropenic patients had significantly diverse. However, there were scanty reports of microbiota alteration of adult patients with acute myeloid leukemia (AML). Stool samples of each treatment-naïve AML patient were collected at the day before induction chemotherapy initiation (pretreatment), first day of neutropenic fever and first day of bone marrow recovery. Bacterial DNA was extracted from stool and sequenced bacterial 16s ribosomal RNA genes by next-generation sequencing. Relative abundance, overall richness, Shannon’s diversity index and Simpson’s diversity index were calculated. Ten cases of AML patients (4 men and 6 women) were included with median age of 39 years (range: 19-49) and all of patients developed febrile neutropenia. Firmicutes were dominated over the period of neutropenic fever and subsequent declined after bone marrow recovery contrast to Bacteroidetes and Proteobacteria.Enterococcuswas more abundant at febrile neutropenia period compared to pretreatment whileBacteroidesandEscherichiawas notably declined during the febrile neutropenia. At the operational taxonomic units (OTUs) level, there was significant higher level of overall richness of pretreatment period than febrile neutropenic episode. Both of the diversity indexes of Shannon and Simpson were considerably decreased at febrile neutropenic period. Adult AML patients with first episode of febrile neutropenia after initial intensive chemotherapy demonstrated the significant decrease of gut microbiota diversity and the level of diversity consistently remained constant despite of bone marrow recovery.
Development of nano-emulsions based onAyapana triplinervisfor the control ofAedes aegyptilarvae
Authors: Rodrigues Alex Bruno Lobato , Lopes Rosany Martins , Rabelo Érica Menezes , Tomazi Rosana , Santos Lizandra Lima , Brandão Lethícia Barreto , Faustino Cleidjane Gomes , Farias Ana Luzia Ferreira , dos Santos Cleydson Breno Rodrigues , de Castro Cantuária Patrick , Galardo Allan Kardec Ribeiro , da Silva de Almeida Sheylla Susan Moreira
Published: July 2020

Ayapana triplinervisis a plant species used in traditional medicine and in mystical-religious rituals by traditional communities in the Amazon. The aim of this study is to evaluate the larvicidal activity againstA. aegyptiof nano-emulsions containing essential oils fromA. triplinervismorphotypes, and acute oral toxicity in non-target organism. Essential oils were identified and nano-emulsions were prepared using the low energy method. The mortality test ofA. aegyptilarvae was performed according to the protocol recommended by the World Health Organization, and toxicity in non-target mammals was performed according to the OECD. Phytochemical analyses indicated the major compounds (E)-Caryophyllene (45.93%) and Thymohydroquinone Dimethyl Ether (32.93%) in morphotype A, and in morphotype B, Thymohydroquinone Dimethyl Ether (84.53%) was found. Morphotype A essential oil nano-emulsion showed a particle size of 101.400 ± 0.971 nm (PdI = 0.124 ± 0.009 and ZP = −19,300 ± 0.787 mV). Morphotype B essential oil nano-emulsion had a particle size of 104.567 ± 0.416 nm (PdI = 0.168 ± 0.016 and ZP = −27,700 ± 1,307 mV). Histomorphological analyses showed the presence of inflammatory cells in the liver of animals treated with morphotype A essential oil nano-emulsion (MAEON) and morphotype B essential oil nano-emulsion (MBEON). Congestion and the presence of transudate with leukocyte infiltration in the lung of animals treated with MAEON were observed. The nano-emulsions containing essential oils ofA. triplinervismorphotypes showed an effective nanobiotechnological product in the chemical control ofA. aegyptilarvae and safe for non-target mammals.
A rational approach to identifying effective combined anticoronaviral therapies against feline coronavirus
Authors: Cook S.E. , Vogel H. , Castillo D. , Olsen M. , Pedersen N. , Murphy B. G.
Published: July 2020

Feline infectious peritonitis (FIP), caused by a genetic mutant of feline enteric coronavirus known as FIPV, is a highly fatal disease of cats with no currently available vaccine or FDA-approved cure. Dissemination of FIPV in affected cats results in a range of clinical signs including cavitary effusions, anorexia, fever and lesions of pyogranulomatous vasculitis and peri-vasculitis with or without central nervous system and/or ocular involvement. There is a critical need for effective and approved antiviral therapies against coronaviruses including FIPV and zoonotic coronaviruses such as SARS-CoV-2, the cause of COVID-19. With regards to SARS-CoV-2, preliminary evidence suggests that there may be potential clinical and pathological overlap with feline coronaviral disease including enteric and neurological involvement in some cases. We have screened 89 putative antiviral compounds and have identified 25 compounds with antiviral activity against FIPV, representing a variety of drug classes and mechanisms of antiviral action. Based upon successful combination treatment strategies for human patients with HIV or hepatitis C virus infections, we have identified combinations of drugs targeting different steps of the FIPV life cycle resulting in synergistic antiviral effect. Translationally, we suggest that a combined anticoronaviral therapy (cACT) with multiple mechanisms of action and penetration of all potential anatomic sites of viral infection should be applied towards other challenging to treat coronaviruses, like SARS-CoV-2.

Author summary

We have screened 89 compoundsin vitrofor antiviral activity against FIPV. The putative antiviral activity of these compounds was either purported to be a direct effect on viral proteins involved in viral replication or an indirect inhibitory effect on normal cellular pathways usurped by FIPV to aid viral replication. Twenty-five of these compounds were found to have significant antiviral activity. Certain combinations of these compounds were determined to be superior to monotherapy alone.
VAMP3 and VAMP8 regulate the development and functionality of parasitophorous vacuoles housingLeishmania amazonensis
Authors: Séguin Olivier , Mai Linh Thuy , Whiteheart Sidney W. , Stäger Simona , Descoteaux Albert
Published: July 2020

To colonize mammalian phagocytic cells, the parasiteLeishmaniaremodels phagosomes into parasitophorous vacuoles that can be either tight-fitting individual or communal. The molecular and cellular bases underlying the biogenesis and functionality of these two types of vacuoles are poorly understood. In this study, we investigated the contribution of host cell Soluble N-ethylmaleimide-sensitive-factor Attachment protein REceptor proteins in the expansion and functionality of communal vacuoles as well as on the replication of the parasite. The differential recruitment patterns of Soluble N-ethylmaleimide-sensitive-factor Attachment protein REceptor to communal vacuoles harboringL. amazonensisand to individual vacuoles housingL. majorled us to further investigate the contribution of VAMP3 and VAMP8 in the interaction ofLeishmaniawith its host cell. We show that whereas VAMP8 contributes to optimal expansion of communal vacuoles, VAMP3 negatively regulatesL. amazonensisreplication, vacuole size, as well as antigen cross-presentation. In contrast, neither proteins has an impact on the fate ofL. major. Collectively, our data support a role for both VAMP3 and VAMP8 in the development and functionality ofL. amazonensis-harboring communal parasitophorous vacuoles.
Biomolecular condensates amplify mRNA decapping by coupling protein interactions with conformational changes in Dcp1/Dcp2
Authors: Tibble Ryan W. , Depaix Anaïs , Kowalska Joanna , Jemielity Jacek , Gross John D.
Published: July 2020

Cells organize biochemical processes into biological condensates. P-bodies are cytoplasmic condensates enriched in factors important for mRNA degradation. P-bodies have been identified as sites of both mRNA storage and decay, but how these opposing outcomes may be achieved in condensates is unresolved. A critical step in mRNA degradation is removal of the 5’-7-methylguanosine cap by Dcp1/Dcp2, which is highly enriched in P-bodies. Dcp1/Dcp2 activity is repressed in condensatesin vitroand requires the activator Edc3. Activation of decapping is amplified in condensates relative to the surrounding solution due to stabilization of an autoinhibited state in Dcp1/Dcp2. Edc3 couples a conformational change in the Dcp1/Dcp2 active site with alteration of the protein-protein interactions driving phase separation to activate decapping in condensates. The composition-dependent regulation of enzyme activity in condensates occurs over length scales ranging from microns to Ångstroms and may control the functional state of P-bodies and related phase-separated compartments.

HIGHLIGHTS

mRNA decapping in droplets is repressed

Catalytically inert droplets are activated by a change in condensate composition

A switch in enzymatic activity requires a conformational change in condensates

Condensates amplify enzyme activation compared to surrounding solution
Several complementary methods of plant establishment are required for effective restoration of banksia woodland
Authors: Brundrett Mark , Wisolith Anna , Collins Margaret , Longman Vanda , Clarke Karen
Published: July 2020

New banksia woodland vegetation was established at two sites totalling 50 ha in the Perth region of Western Australia as part of an offset-funded project. Restoration methods included topsoil transfer (16 ha), planting of nursery-raised local provenance seedlings (46,000 seedlings over 39.5 ha) and direct seeding with machinery or by hand (16.5 ha) with treatments overlapped. Six years of rigorous monitoring revealed trends in plant diversity, density and cover and allowed comparison of vegetation structure and composition to reference sites. Of the 162 native plants recorded, 115 originated primarily from the topsoil seed bank and the remainder from planting and seeding. Native plant germination from topsoil peaked at 700,000 stems per ha in year 2, but there was very high attrition during extreme summer drought. By year 5, native perennials averaged 20,000 stems per ha, well above the target of 7,000, but there was high spatial variability in plant density with 1/3 of quadrats below target. Saplings of Banksia spp. (the dominant local trees) plateaued at 150-220 stems per ha due to high summer mortality. Native plant cover reached 20% and perennial weed cover stabilised at under 5% within 5 years. Several complimentary methods were required for successful restoration, since transferred topsoil established most of the plant diversity. However, trees required planting or seeding, due to their canopy stored seed. Direct seeding and planting without respread topsoil led to lower overall diversity and density, but higher tree density. Most completion criteria targets were reached after 5 years. Areas with respread topsoil are trending towards recovery as a banksia woodland, but areas with only planting and seeding are likely to remain a separate vegetation type. Evidence for resilience of restored areas was provided by abundant pollination and seed set and second-generation seedlings. We suggest it may be possible to restore banksia woodland despite major challenges due to unpredictable offset funding, climate, weeds, grazing, recalcitrant species, and seed availability, but long-term monitoring is required to confirm this.
Spontaneous social communication in laboratory mice - placing ultrasonic vocalizations in their behavioral context
Authors: Ey Elodie , de Chaumont Fabrice , Bourgeron Thomas
Published: July 2020

In their natural habitat, mice interact and communicate to regulate major functions, such as reproduction, group coordination, and protection. Nevertheless, little is currently known about their spontaneous emission of ultrasonic vocalizations (USVs), despite their broad use as a phenotypic marker in mouse models of neuropsychiatric disorders. Here, we investigated mouse spontaneous communication by coupling automatic recording, segmentation, and analysis of USVs to the tracking of complex behaviors. We continuously recorded undisturbed same-sex pairs of C57BL/6J males and females at 5 weeks and 3 and 7 months of age over three days. Males emitted only a few short USVs, mainly when isolated from their conspecific, whereas females emitted a high number of USVs, especially when engaged in intense dynamic social interactions. The context-specific use of call types and acoustic variations emerged with increasing age. The emission of USVs also reflected a high level of excitement in social interactions. Finally, mice lacking Shank3, a synaptic protein associated with autism, displayed atypical USV usage and acoustic structure, which did not appear in classical protocols, highlighting the importance of studying spontaneous communication. The methods are freely available for the research community (https://usv.pasteur.cloud).
Aversion encoded in the subthalamic nucleus
Authors: Serra Gian Pietro , Guillaumin Adriane , Baufreton Jérome , Georges François , Wallén-Mackenzie Åsa
Published: July 2020

Activation of the subthalamic nucleus (STN) is associated with the stopping of ongoing behavior via the basal ganglia. However, we recently observed that optogenetic STN excitation induced a strong jumping/escaping behavior. We hypothesized that STN activation is aversive. To test this, place preference was assessed. Optogenetic excitation of the STN caused potent place aversion. Causality between STN activation and aversion has not been demonstrated previously. The lateral habenula (LHb) is a critical hub for aversion. Optogenetic stimulation of the STN indeed caused firing of LHb neurons, but with delay, suggesting the involvement of a polysynaptic circuit. To unravel a putative pathway, the ventral pallidum (VP) was investigated. VP receives projections from the STN and in turn projects to the LHb. Optogenetic excitation of STN-VP terminals caused firing of VP neurons and induced aversive behavior. This study identifies the STN as critical hub for aversion, potentially mediated via an STN-VP-LHb pathway.
Both default and multiple-demand regions represent semantic goal information
Authors: Wang Xiuyi , Gao Zhiyao , Smallwood Jonathan , Jefferies Elizabeth
Published: July 2020

While the multiple-demand network plays an established role in cognitive flexibility, the role of default mode network is more poorly understood. In this study, we used a semantic feature matching task combined with multivoxel pattern decoding to test contrasting functional accounts. By one view, default mode and multiple-demand networks have opposing roles in cognition; consequently, while multiple-demand regions can decode current goal information, semantically-relevant default network regions might decode conceptual similarity irrespective of task demands. Alternatively, default mode regions might show sensitivity to changing task demands like multiple-demand regions, consistent with evidence that both networks dynamically alter their patterns of connectivity depending on the context. Our task required participants to integrate conceptual knowledge with changing task goals, such that successive decisions were based on different features of the items (colour, shape and size). This allowed us to simultaneously decode semantic category and current goal information using a whole-brain searchlight decoding approach. As expected, multiple-demand regions represented information about the currently-relevant conceptual feature, yet similar decoding results were found in default mode network regions, including angular gyrus and posterior cingulate cortex. Semantic category irrespective of task demands could be decoded in lateral occipital cortex, but not in most regions of default mode network. These results show that conceptual information related to the current goal dominates the multivariate response within default mode network. In this way, default mode network nodes support flexible memory retrieval by modulating their response to suit active task goals, alongside regions of multiple-demand cortex.

Significance Statement

We tested contrasting accounts of default mode network (DMN) function using multivoxel pattern analysis. By one view, semantically-relevant parts of DMN represent conceptual similarity, irrespective of task context. By an alternative view, DMN tracks changing task demands. Our semantic feature matching task required participants to integrate conceptual knowledge with task goals, such that successive decisions were based on different features of the items. We demonstrate that DMN regions can decode current goal, alongside multiple-demand regions traditionally associated with cognitive control. The successful decoding of goal information plus largely absent category decoding effects within DMN indicates that this network supports flexible semantic cognition.
The cysteine-rich exosporium morphogenetic protein, CdeC, exhibits self-assembly properties that lead to organized inclusion bodies inEscherichia coli
Authors: Romero-Rodríguez A. , Troncoso-Cotal S. , Guerrero-Araya E. , Paredes-Sabja D.
Published: July 2020

Clostridioides difficileis an obligate anaerobe spore-forming, Gram-positive, pathogenic bacterium, considered the leading cause of nosocomial diarrhea worldwide. Recent studies have attempted to understand the biology of the outer-most layer ofC. difficilespores, the exosporium, which is believed to contribute to early interactions with the host. The fundamental role of the cysteine-rich proteins CdeC and CdeM has been described. However, the molecular details behind the mechanism of exosporium assembly are missing. The underlying mechanisms that govern exosporium assembly inC. difficileremain poorly studied, in part due to difficulties in obtaining pure soluble recombinant proteins of theC. difficileexosporium. In this work, we observed that CdeC was able to form organized inclusion bodies in theE. coliBL21 (DE3) pRIL strain filled with lamellae-like structures separated by an interspace of 5-15 nm; however, this lamellae-like organization is lost upon overexpression inE. coliSHuffle T7 strain with an oxidative environment. Additionally, DTT treatment of CdeC inclusion bodies released monomeric soluble forms of CdeC. Three truncated versions of the CdeC protein were constructed. While all the variants were able to aggregate forming oligomers that are resistant to denaturation conditions, TEM micrographs suggest that the self-organization properties of CdeC may be attributed to the C-terminal domain. Overall, these observations have important implications in further studies implicated in elucidating the role of CdeC in the exosporium assembly ofC. difficilespores.
Structural insight into hormone recognition and transmembrane signaling by the atrial natriuretic peptide receptor
Authors: Ogawa Haruo , Kodama Masami , Izumikawa Kei
Published: July 2020

Atrial natriuretic peptide (ANP) is an endogenous and potent hypotensive hormone that elicits natriuretic, diuretic, vasorelaxant, and anti-proliferative effects, which play a central role in the regulation of blood pressure and volume. To investigate the hormone-binding and membrane signaling mechanisms mediated by the ANP receptor, we elucidated the crystal structures of the ANP receptor extracellular hormone-binding domain (ANPR) complexed with full-length ANP, truncated mutants of ANP, and dendroaspis natriuretic peptide (DNP) isolated from the venom of the green Mamba snake,Dendroaspis angusticeps. The bound peptides possessed pseudo two-fold symmetry to which the tight coupling of the peptide to the receptor and guanylyl cyclase activity was attributed. The crystal structures and our results from kinetic experiments provide insight into the ligand recognition and transmembrane signaling mechanism of the ANP receptor. Our findings provide useful information that can be applied to drug discovery for heart failure therapies.
Genetic manipulation of the optical refractive index in living cells
Authors: Ogawa Junko , Iwata Yoko , Tonnu Nina U , Gopinath Chitra , Huang Ling , Itoh Sachihiko , Ando Ryoko , Miyawaki Atsushi , Verma Inder M , Pao Gerald M
Published: July 2020

The optical refractive index of cellular components is generally not a property considered amenable to manipulation in microscopy as this is an intrinsic physical property of materials. Here we show that by targeting cephalopod reflectin protein nanoparticles one can manipulate the optical refractive index of mammalian cellular compartments. We further demonstrate that refractive index alteration based contrast agents can be utilized for dark field microscopy and quantitative phase contrast holotomography. Additionally we have molecularly cloned novel reflectins with improved and novel optical properties.