bluuebunny/crossref_metadata_2025 huggingface dataset:
Tryptophan plays an important role in yeast’s tolerance to isobutanol
Authors: Liu Hsien-Lin , Wang Christine H.-T. , Chiang En-Pei Isabel , Huang Chieh-Chen , Li Wen-Hsiung
Published: October 2021

Background

Isobutanol is considered a potential biofuel, thanks to its high-energy content and octane value, limited water solubility, and compatibility with gasoline. As its biosynthesis pathway is known, a microorganism, such as Saccharomyces cerevisiae, that inherently produces isobutanol, can serve as a good engineering host. Isobutanol’s toxicity, however, is a major obstacle for bioproduction. This study is to understand how yeast tolerates isobutanol.

Results

A S. cerevisiae gene-deletion library with 5006 mutants was used to screen genes related to isobutanol tolerance. Image recognition was efficiently used for high-throughput screening via colony size on solid media. In enrichment analysis of the 161 isobutanol-sensitive clones identified, more genes than expected were mapped to tryptophan biosynthesis, ubiquitination, and the pentose phosphate pathway (PPP). Interestingly, adding exogenous tryptophan enabled both tryptophan biosynthesis and PPP mutant strains to overcome the stress. In transcriptomic analysis, cluster analysis of differentially expressed genes revealed the relationship between tryptophan and isobutanol stress through some specific cellular functions, such as biosynthesis and transportation of amino acids, PPP, tryptophan metabolism, nicotinate/nicotinamide metabolism (e.g., nicotinamide adenine dinucleotide biosynthesis), and fatty acid metabolism.

Conclusions

The importance of tryptophan in yeast’s tolerance to isobutanol was confirmed by the recovery of isobutanol tolerance in defective strains by adding exogenous tryptophan to the growth medium. Transcriptomic analysis showed that amino acid biosynthesis- and transportation-related genes in a tryptophan biosynthesis-defective host were up-regulated under conditions similar to nitrogen starvation. This may explain why ubiquitination was required for the protein turnover. PPP metabolites may serve as precursors and cofactors in tryptophan biosynthesis to enhance isobutanol tolerance. Furthermore, the tolerance mechanism may also be linked to tryptophan downstream metabolism, including the kynurenine pathway and nicotinamide adenine dinucleotide biosynthesis. Both pathways are responsible for cellular redox balance and anti-oxidative ability. Our study highlights the central role of tryptophan in yeast’s isobutanol tolerance and offers new clues for engineering a yeast host with strong isobutanol tolerance.
Aedes aegypti: egg morphology and embryonic development
Authors: Mundim-Pombo Ana Paula Miranda , Carvalho Hianka Jasmyne Costa de , Rodrigues Ribeiro Rafaela , León Marisol , Maria Durvanei Augusto , Miglino Maria Angélica
Published: October 2021

Background

The diseases for whichAedes aegyptiis a vector are worrisome. The high vector competence of this mosquito, as well as its anthropophilia and ability to adapt to the urban environment, allows it to exploit many habitats, making its prevention an arduous task. Despite current disease control measures focused on the mosquito, the effectiveness in containing its dispersion still requires improvement; thus greater knowledge about this insect is fundamental.

Methods

Aedes aegypti egg morphology and embryonic development were analyzed from eggs of the insectary of the Institute of Biomedical Sciences of the University of São Paulo. Optical (light and confocal) and electronic (transmission and scanning) microscopy were used to analyze the morphological and ultrastructural features of the eggs. Embryos were observed in the initial (0–20.5 h after egg-laying), intermediate (20.6–40.1 h after egg-laying), and final (40.2–61.6 h) stages of development, and kept at a temperature of 28 °C ± 1 °C until collection for processing.

Results

Eggs ofAe. aegyptiwere whitish at the time of oviposition, and then quickly became black. The egg length was 581.45 ± 39.73 μm and the width was 175.36 ± 11.59. Access to the embryo was difficult due to the egg morphology, point of embryonic development, and difficult permeability of the exochorion (mainly in fixation). Only about 5% of the collected eggs were successfully processed. In the initial stage of embryonic development, characteristics suggestive of intense cellular activity were found. In the intermediate stage, the beginning of the segmentation process was evident. In the final phase, it was possible to differentiate the cephalic region and the thoracic and abdominal segments.

Conclusion

The chorion was found to be an important protective barrier and a limiting factor for the evaluation of the embryos and mosquito embryonic cells, indicating that further studies need to be carried out to identify the reason that this occurs.

Graphical abstract
Bacteroides vulgatus and Bacteroides dorei predict immune-related adverse events in immune checkpoint blockade treatment of metastatic melanoma
Authors: Usyk Mykhaylo , Pandey Abhishek , Hayes Richard B. , Moran Una , Pavlick Anna , Osman Iman , Weber Jeffrey S. , Ahn Jiyoung
Published: October 2021

Background

Immune checkpoint blockade (ICB) shows lasting benefits in advanced melanoma; however, not all patients respond to this treatment and many develop potentially life-threatening immune-related adverse events (irAEs). Identifying individuals who will develop irAEs is critical in order to improve the quality of care. Here, we prospectively demonstrate that the gut microbiome predicts irAEs in melanoma patients undergoing ICB.

Methods

Pre-, during, and post-treatment stool samples were collected from 27 patients with advanced stage melanoma treated with IPI (anti-CTLA-4) and NIVO (anti-PD1) ICB inhibitors at NYU Langone Health. We completed 16S rRNA gene amplicon sequencing, DNA deep shotgun metagenomic, and RNA-seq metatranscriptomic sequencing. The divisive amplicon denoising algorithm (DADA2) was used to process 16S data. Taxonomy for shotgun sequencing data was assigned using MetaPhlAn2, and gene pathways were assigned using HUMAnN 2.0. Compositionally aware differential expression analysis was performed using ANCOM. The Cox-proportional hazard model was used to assess the prospective role of the gut microbiome (GMB) in irAES, with adjustment for age, sex, BMI, immune ICB treatment type, and sequencing batch.

Results

Two natural GMB clusters with distinct community compositions were identified from the analysis of 16S rRNA data (R2= 0.16,p< 0.001). In Cox-proportional hazard modeling, these two clusters showed a near 7-fold differential risk for developing irAEs within 1 year of initiating treatment (HR = 6.89 [95% CI: 1.33–35.58]). Using shotgun metagenomics, we further identified 37 bacterial strains differentially expressed between the risk groups, with specific dominance ofBacteroides doreiwithin the high-risk GMB cluster andBacteroides vulgatusin the low-risk cluster. The high-risk cluster also appeared to have elevated expression of several functional pathways, including those associated with adenosine metabolism (all FDR < 0.05). A sub-analysis of samples (n= 10 participants) at baseline and 6 and 12 weeks after the start of treatment revealed that the microbiome remained stable over the course of treatment (R2= 0.88,p< 0.001).

Conclusions

We identified two distinct fecal bacterial community clusters which are associated differentially with irAEs in ICB-treated advanced melanoma patients.
Intra-patient stability of tumor mutational burden from tissue biopsies at different time points in advanced cancers
Authors: Pham Timothy V. , Goodman Aaron M. , Sivakumar Smruthy , Frampton Garrett , Kurzrock Razelle
Published: October 2021

Background

Tumor mutational burden (TMB) may be a predictive biomarker of immune checkpoint inhibitor (ICI) responsiveness. Genomic landscape heterogeneity is a well-established cancer feature. Molecular characteristics may differ even within the same tumor specimen and undoubtedly evolve with time. However, the degree to which TMB differs between tumor biopsies within the same patient has not been established.

Methods

We curated data on 202 patients enrolled in the PREDICT study (NCT02478931), seen at the University of California San Diego (UCSD), who had 404 tissue biopsies for TMB (two per patient, mean of 722 days between biopsies) to assess difference in TMB before and after treatment in a pan-cancer cohort. We also performed an orthogonal analysis of 2872 paired pan-solid tumor biopsies in the Foundation Medicine database to examine difference in TMB between first and last biopsies.

Results

The mean (95% CI) TMB difference between samples was 0.583 [− 0.900–2.064] (p = 0.15). Pearson correlation showed a flat line for time elapsed between biopsies versus TMB change indicating no correlation (R2 = 0.0001; p = 0.8778). However, in 55 patients who received ICIs, there was an increase in TMB (before versus after mean mutations/megabase [range] 12.50 [range, 0.00–98.31] versus 14.14 [range, 0.00–100.0], p = 0.025). Analysis of 2872 paired pan-solid tumor biopsies in the Foundation Medicine database also indicated largely stable TMB patterns; TMB increases were only observed in specific tumors (e.g., breast, colorectal, glioma) within certain time intervals.

Conclusions

Overall, our results suggest that tissue TMB remains stable with time, though specific therapies such as immunotherapy may correlate with an increase in TMB.

Trial registration

NCT02478931, registered June 23, 2015.
There is a world beyond αvβ3-integrin: Multimeric ligands for imaging of the integrin subtypes αvβ6, αvβ8, αvβ3, and α5β1 by positron emission tomography
Authors: Steiger Katja , Quigley Neil Gerard , Groll Tanja , Richter Frauke , Zierke Maximilian Alexander , Beer Ambros Johannes , Weichert Wilko , Schwaiger Markus , Kossatz Susanne , Notni Johannes
Published: October 2021

Background

In the context of nuclear medicine and theranostics, integrin-related research and development was, for most of the time, focused predominantly on 'RGD peptides' and the subtype αvβ3-integrin. However, there are no less than 24 known integrins, and peptides without the RGD sequence as well as non-peptidic ligands play an equally important role as selective integrin ligands. On the other hand, multimerization is a well-established method to increase the avidity of binding structures, but multimeric radiopharmaceuticals have not made their way into clinics yet. In this review, we describe how these aspects have been interwoven in the framework of the German Research Foundation's multi-group interdisciplinary funding scheme CRC 824, yielding a series of potent PET imaging agents for selective imaging of various integrin subtypes.

Results

The gallium-68 chelator TRAP was utilized to elaborate symmetrical trimers of various peptidic and non-peptidic integrin ligands. Preclinical data suggested a high potential of the resulting Ga-68-tracers for PET-imaging of the integrins α5β1, αvβ8, αvβ6, and αvβ3. For the first three, we provide some additional immunohistochemistry data in human cancers, which suggest several future clinical applications. Finally, application of αvβ3- and αvβ6-integrin tracers in pancreatic carcinoma patients revealed that unlike αvβ3-targeted PET, αvβ6-integrin PET is not characterized by off-target uptake and thus, enables a substantially improved imaging of this type of cancer.

Conclusions

Novel radiopharmaceuticals targeting a number of different integrins, above all, αvβ6, have proven their clinical potential and will play an increasingly important role in future theranostics.
Current knowledge and challenges associated with targeted delivery of neurotrophic factors into the central nervous system: focus on available approaches
Authors: Bahlakeh Gozal , Rahbarghazi Reza , Mohammadnejad Daruosh , Abedelahi Ali , Karimipour Mohammad
Published: October 2021

During the last decades, numerous basic and clinical studies have been conducted to assess the delivery efficiency of therapeutic agents into the brain and spinal cord parenchyma using several administration routes. Among conventional and in-progress administrative routes, the eligibility of stem cells, viral vectors, and biomaterial systems have been shown in the delivery of NTFs. Despite these manifold advances, the close association between the delivery system and regeneration outcome remains unclear. Herein, we aimed to discuss recent progress in the delivery of these factors and the pros and cons related to each modality.
Predictors of adherence to an internet-based cognitive behavioral therapy program for individuals with chronic pain and comorbid psychological distress
Authors: Gasslander Nils , Alfonsson Sven , Jackalin Amanda , Tengberg Cecilia , Håkansson Johanna , Huotari Linda , Buhrman Monica
Published: October 2021

Background

The burden caused by chronic pain is significant, affecting at least 10 percent of the world´s population. While internet-based treatments based on cognitive behavioral therapy (CBT) have been shown to be promising in this area, attrition levels vary significantly. The purpose of this study was to investigate predictor variables for participants’ adherence to an internet-based CBT treatment for individuals with chronic pain as well as to investigate associations between adherence and treatment outcome.

Methods

Data for this study was retrieved from a randomized controlled trial including 95 individuals with chronic pain who received internet-based CBT. Treatment adherence was studied through three outcome variables: treatment progress, treatment completion and exercise completion. The predictor variables were grouped into four clusters: background variables (age, gender, marital status, level of education, and typical computer usage); the second cluster included health status variables (sick leave, current psychiatric diagnosis, previous psychotherapy for pain, current pharmacological treatment, previous depression, current depression, and current depressive symptoms); the third cluster included pain-related variables (opioid medication, history of pain, and pain symptoms) and the fourth cluster included motivation variables (measured with treatment preference, treatment credibility, compliance to the treatment schedule and contact with the therapists).

Results

Findings showed that treatment progress was predicted by higher treatment credibility at baseline, whereas participants who were behind schedule in the second week of the program finished fewer treatment modules. When analyzing each cluster of predictor variables separately, current depressive symptoms also predicted fewer completed treatment modules.Among the pain-related variables, higher pain acceptance was the only predictor for completing more treatment modules. Treatment completion (which in this study was defined as having completed at least 75% of treatment modules) was predicted by higher treatment credibility and fewer depressive symptoms at baseline, and was thus similar to the results regarding treatment progress. Finally, all adherence variables predicted the treatment outcome pain interference.

Conclusions

Low treatment credibility, depressive symptoms and falling behind the treatment schedule early on were the most important predictor variables for low treatment adherence, while a number of demographical and pain-related variables were not related to adherence. The results from this study may help clinicians identify patients who are less likely to complete, and thus benefit from, their pain treatment.

Trial registrationClinicalTrials.gov NTC03316846.
Writing group program reduces academic procrastination: a quasi-experimental study
Authors: Patria Bhina , Laili Latifatul
Published: October 2021

Background

Procrastination is a common problem in higher education. It leads to negative consequences on students’ health and academic achievement. Nevertheless, research concerning interventions has not yet produced consistent results. This study aims to examine the effectiveness of a writing group program on reducing academic procrastination.

Methods

This study was a quasi-experimental study with a one-group pretest-posttest design using double pretests. A double pretest design was used to ensure the internal validity of the experiment. Twenty graduate students followed a 15-days writing group program consisted of a training session and four sessions of writing groups. A thesis procrastination scale was used to measure the intervention’s effects.

Results

The writing group program helped students to set a writing target, discussed writing progress, and provided social support to their colleagues. The results showed that the intervention program could significantly decrease academic procrastination.

Conclusion

The present study demonstrated that a writing group could potentially reduce academic procrastination. Thus, students could benefit from a writing group when working on their master thesis. A thesis preparation course that provides information about goal-setting strategy and the principles of effective writing habits (i.e., behavioral, artisanal, social and emotional habits), might also assist students in writing their thesis. Further research is needed, preferably through the provision of a control group, a randomized assignment and a larger sample.
Highly accurate and efficient two phase-intrusion detection system (TP-IDS) using distributed processing of HADOOP and machine learning techniques
Authors: Jadhav Abhijit Dnyaneshwar , Pellakuri Vidyullatha
Published: October 2021

Network security and data security are the biggest concerns now a days. Every organization decides their future business process based on the past and day to day transactional data. This data may consist of consumer’s confidential data, which needs to be kept secure. Also, the network connections when established with the external communication devices or entities, a care should be taken to authenticate these and block the unwanted access. This consists of identification of the malicious connection nodes and identification of normal connection nodes. For that, we use a continuous monitoring of the network input traffic to recognize the malicious connection request called as intrusion and this type of monitoring system is called as an Intrusion detection system (IDS). IDS helps us to protect our network and data from insecure and malicious network connections. Many such systems exists in the real time scenario, but they have critical issues of performance like accuracy and efficiency. These issues are addressed as a part of this research work of IDS using machine learning techniques and HDFS. The TP-IDS is designed in two phases for increasing accuracy. In phase I of TP-IDS, Support Vector Machine (SVM) and k Nearest Neighbor (kNN) are used. In phase II of TP-IDS, Decision Tree (DT) and Naïve Bayes (NB) are used, where phase II is the validation phase of the system for increasing accuracy. Also, both the phases are having Hadoop distributed file system underlying data storage and processing architecture, which allows parallel processing to increase the speed of the system and hence achieve the efficiency in TP-IDS.
Biological and synthetic approaches to inhibiting nitrification in non-tilled Mediterranean soils
Authors: Bozal-Leorri Adrián , Corrochano-Monsalve Mario , Arregui Luis Miguel , Aparicio-Tejo Pedro M. , González-Murua Carmen
Published: October 2021

Background

The increasing demand for food production has led to a tenfold increase in nitrogen (N) fertilizer use since the Green Revolution. Nowadays, agricultural soils have been turned into high-nitrifying environments that increase N pollution. To decrease N losses, synthetic nitrification inhibitors (SNIs) such as 3,4-dimethylpyrazole phosphate (DMPP) have been developed. However, SNIs are not widely adopted by farmers due to their biologically limited stability and soil mobility. On the other hand, allelopathic substances from root exudates from crops such as sorghum are known for their activity as biological nitrification inhibitors (BNIs). These substances are released directly into the rhizosphere. Nevertheless, BNI exudation could be modified or even suppressed if crop development is affected. In this work, we compare the performance of biological (sorghum crop) and synthetic (DMPP) nitrification inhibitors in field conditions.

Results

Sorghum crop BNIs and DMPP prevented an increase in the abundance of ammonia-oxidizing bacteria (AOB) without affecting the total bacterial abundance. Both nitrification inhibitors maintained similar soil NH4+content, but at 30 days post-fertilization (DPF), the sorghum BNIs resulted in higher soil NO3−content than DMPP. Even so, these inhibitors managed to reduce 64% and 96%, respectively, of the NO3−-N/NH4+-N ratio compared to the control treatment. Similar to soil mineral N, there were no differences in leaf δ15N values between the two nitrification inhibitors, yet at 30 DPF, δ15N values from sorghum BNI were more positive than those of DMPP. N2O emissions from DMPP-treated soil were low throughout the experiment. Nevertheless, while sorghum BNIs also maintained low N2O emissions, they were associated with a substantial N2O emission peak at 3 DPF that lasted until 7 DPF.

Conclusions

Our results indicate that while sorghum root exudates can reduce nitrification in field soil, even at the same efficiency as DMPP for a certain amount of time, they are not able to prevent the N pollution derived from N fertilization as DMPP does during the entire experiment.

Graphic Abstract
Development and application of a chemical profiling method for the assessment of the quality and consistency of the Pelargonium sidoides extract
Authors: Yu Se Mi , Kim Sung Jun , Yoon Yeong Cheol , Kim Jong Hoon
Published: October 2021

The evaluation of chemical similarity is very significant for the evaluation and standardization of the quality of herbal medicines as the biological activity of herbal medicines depends on the composition and proportion of many individual components. Many health organizations have recommended chemical profiling for the quality and consistency evaluation of herbal medicines. In this study, chemical profiling was performed to evaluate the similarity between batches of Pelargonium sidoides maltodextrin mixture (PMM) from EPs® 7630, a Pelargonium sidoides extract preparation. For chemical profile analysis, 7 common peaks were selected from 27 different PMM batches and specificity, linearity, accuracy, and precision tests were performed to develop the analytical method. The Pearson correlation coefficients of the similarity for all 27 batches manufactured over the years were higher than 0.90, indicating that quality consistency is well ensured over the years. This profiling method confirms the chemical profile of various commercial products using not only PMM but also Pelargonium sidoides extract and shows that it can be applied to standardization of quality.
FDG-PET/CT imaging for evaluating durable responses to immune check point inhibitors in patients with advanced cutaneous squamous cell carcinoma
Authors: McLean Luke S. , Cavanagh Karda , Hicks Rodney J. , Callahan Jason , Xie Jing , Cardin Anthony , Lim Annette M. , Rischin Danny
Published: October 2021

Background

The role of FDG-PET/CT imaging in assessing response to immunotherapy in advanced cutaneous squamous cell carcinoma (CSCC) is unknown. This study compared complete metabolic response (CMR) rates by FDG-PET and RECIST1.1 via CT or MRI in patients on cemiplimab for > 10 months.

Methods

This was a single-centre retrospective study of 15 patients treated with cemiplimab for advanced CSCC who had CT/MRI and FDG-PET/CT at > 10 months to assess metabolic treatment response. The median age was 73 years (range 55–84) and 93% were male. RECIST1.1 and PERCIST1.0 tumor responses were evaluated by blinded readers.

Results

Seventy-three percent (11/15) (95%CI 44.9, 92.2%) achieved a CMR on PET. Of these 11, on RECIST1.1 there was one complete response, 9 partial responses and one stable disease.

Conclusions

In patients on cemiplimab for > 10 months, there was discordance between CR rates on FDG-PET versus RECIST1.1. FDG-PET/CT may have utility for clarifying depth of response in patients treated with immunotherapy for CSCC.
Supporting self-management and clinic attendance in young adults with type 1 diabetes: development of the D1 Now intervention
Authors: Morrissey Eimear C. , Casey Bláthín , Hynes Lisa ,   The D1 Now Young Adult Panel, Dinneen Sean F. , Byrne Molly
Published: October 2021

Background

Self-management of type 1 diabetes (T1D) is complex and can be particularly challenging for young adults. This is reflected in the high blood glucose values and rates of clinic non-attendance in this group. There is a gap for a theory-based intervention informed by key stakeholder opinions to support and improve self-management in young adults with T1D.

Purpose

The aim of the work was to systematically co-develop an evidence-based and stakeholder-led intervention to support self-management and clinic engagement in young adults living with T1D in Ireland. Co-development was led by the Young Adult Panel.

Methods

The Behaviour Change Wheel was used to guide the development. Five evidence sources were used to inform the process. An iterative co-design process was used with the Young Adult Panel. Initial intervention components were refined and feasibility tested using qualitative methods.

Results

Environmental restructuring, education and training were selected as appropriate intervention functions. The co-design process, along with qualitative refinement and feasibility work, led to the final intervention content which consisted of 17 behaviour change techniques. The final D1 Now intervention consists of three components: a support worker, an agenda setting tool and an interactive messaging service.

Conclusions

The D1 Now intervention is now at pilot evaluation stage. Its transparent and systematic development will facilitate evaluation and future replications.
Additive role of dynamic subtraction MRI in assessment of unresolved HCC post-radiofrequency ablation
Authors: El-Assaly Hany , Abdallah Mohamed Farouk Hussein , Mohamed Wael Maher , Youssef Mohamed Ibrahim
Published: October 2021

Background

Malignant Hepatocellular carcinoma (HCC) is one amongst the foremost widespread cancers within the world. Radiofrequency ablation (RFA) is that the most generally used substitute tool for hepatic carcinoma treatment. Monitoring tumoral response to loco-regional therapy is a vital mission in oncological imaging. Dynamic contrast enhanced MR and recently added subtraction imaging technique improve assessment of the ablated hepatic focal lesions. The aim of this study is that the evaluation of the role of Subtraction MRI within the detection of recurrent or residual tumoral viability after RF ablation.

Results

Fifty patients were conducted during this retrospective study, all underwent RFA for 76 hepatic focal lesions and underwent Dynamic MRI study 1 month after ablation. Subtraction imaging was then performed. MRI images were interpreted by two readers who are experienced in hepatic imaging. The primary reader interpreted the standard Dynamic MRI and was blinded to the subtraction sequences; the second reader interpreted both Dynamic and Subtraction MRI images. the primary reader detected 49 resolved cases by dynamic MRI, while the second reader detected residual activity in 6 cases out of 49 via subtraction dynamic MRI (added value). The second reader agreed with first reader in 43 cases (agreement).The first reader detected 27 residual cases by dynamic MRI. The second reader disagreed with first reader in 11 cases appeared resolved out of 27 via subtraction dynamic MRI (added value). The second reader agreed with first reader in residual activity in 16 cases (agreement).The statistical analysis of those results revealed a big additive value of the subtraction imaging to the dynamic MRI (P < 0.001) with moderate degree of agreement between the 2 diagnostic tools (Kappa value = 0.491). This implies that Subtraction MRI significantly improves the reader confidence level within the assessment of treatment response following loco-regional therapies for HCC.

Conclusion

Dynamic Subtraction MRI is a powerful detector for real enhancement in treated HCC lesions after radiofrequency ablation and hence increasing the degree of readers’ confidence and accuracy of treated lesions in follow-up studies. So it's recommended to feature this powerful tool as a routine to any or all Dynamic MRI studies of the Liver.
Portrait and Scan
Authors: Grant Jenna
Published: October 2021

This article is an ethnography of color and black-and-white in medical images of a particular kind—prenatal ultrasound—in a particular place—Phnom Penh, Cambodia. It is also a meditation on histories and theorizations of color. It moves from the discourse and practice of pregnant women, family members, and doctors about color and black-and-white, to political and intellectual histories of color in Cambodia and in anthropology, to Buddhist ontologies of pregnancy and life. Across this diverse terrain, the notion of the image-affect conveys how images stimulate affective responses in viewers and how images affect their referents. A method of listening to and for image-affects helps us to understand how people relate to the elemental instability of images and the instability of beings to which images refer and with which they become.
Regulation of NANOG and SOX2 expression by activin A and a canonical WNT agonist in bovine embryonic stem cells and blastocysts
Authors: Xiao Yao , Sosa Froylan , Ross Pablo J. , Diffenderfer Kenneth E. , Hansen Peter J.
Published: October 2021

Bovine embryonic stem cells (ESC) have features associated with the primed pluripotent state including low expression of one of the core pluripotency transcription factors, NANOG. It has been reported that NANOG expression can be upregulated in porcine ESC by treatment with activin A and the WNT agonist CHIR99021. Accordingly, it was tested whether expression of NANOG and another pluripotency factor SOX2 could be stimulated by activin A and the WNT agonist CHIR99021. Immunoreactive NANOG and SOX2 were analyzed for bovine ESC lines derived under conditions in which activin A and CHIR99021 were added singly or in combination. Activin A enhanced NANOG expression but also reduced SOX2 expression. CHIR99021 depressed expression of both NANOG and SOX2. In a second experiment, activin A enhanced blastocyst development while CHIR99021 treatment impaired blastocyst formation and reduced number of blastomeres. Activin A treatment decreased blastomeres in the blastocyst that were positive for either NANOG or SOX2 but increased those that were CDX2+ and that were GATA6+ outside the inner cell mass. CHIR99021 reduced SOX2+ and NANOG+ blastomeres without affecting the number or percent of blastomeres that were CDX2+ and GATA6+. Results indicate activation of activin A signaling stimulates NANOG expression during self-renewal of bovine ESC but suppresses cells expressing pluripotency markers in the blastocyst and increases cells expressing CDX2. Actions of activin A to promote blastocyst development may involve its role in promoting trophectoderm formation. Furthermore, results demonstrate the negative role of canonical WNT signaling in cattle for pluripotency marker expression in ESC and in formation of the inner cell mass and epiblast during embryonic development.

This article has an associated First Person interview with the first author of the paper.
The population frequency of human mitochondrial DNA variants is highly dependent upon mutational bias
Authors: Dunn Cory D.
Published: October 2021

Next-generation sequencing can quickly reveal genetic variation potentially linked to heritable disease. As databases encompassing human variation continue to expand, rare variants have been of high interest, since the frequency of a variant is expected to be low if the genetic change leads to a loss of fitness or fecundity. However, the use of variant frequency when seeking genomic changes linked to disease remains very challenging. Here, I explored the role of selection in controlling human variant frequency using the HelixMT database, which encompasses hundreds of thousands of mitochondrial DNA (mtDNA) samples. I found that a substantial number of synonymous substitutions, which have no effect on protein sequence, were never encountered in this large study, while many other synonymous changes are found at very low frequencies. Further analyses of human and mammalian mtDNA datasets indicate that the population frequency of synonymous variants is predominantly determined by mutational biases rather than by strong selection acting upon nucleotide choice. My work has important implications that extend to the interpretation of variant frequency for non-synonymous substitutions.
An anti-tuberculosis compound screen using a zebrafish infection model identifies an aspartyl-tRNA synthetase inhibitor
Authors: Habjan Eva , Ho Vien Q. T. , Gallant James , van Stempvoort Gunny , Jim Kin Ki , Kuijl Coen , Geerke Daan P. , Bitter Wilbert , Speer Alexander
Published: October 2021

Finding new anti-tuberculosis compounds with convincing in vivo activity is an ongoing global challenge to fight the emergence of multidrug-resistant Mycobacterium tuberculosis isolates. In this study, we exploited the medium-throughput capabilities of the zebrafish embryo infection model with Mycobacterium marinum as a surrogate for M. tuberculosis. Using a representative set of clinically established drugs, we demonstrate that this model could be predictive and selective for antibiotics that can be administered orally. We further used the zebrafish infection model to screen 240 compounds from an anti-tuberculosis hit library for their in vivo activity and identified 14 highly active compounds. One of the most active compounds was the tetracyclic compound TBA161, which was studied in more detail. Analysis of resistant mutants revealed point mutations in aspS (rv2572c), encoding an aspartyl-tRNA synthetase. The target was genetically confirmed, and molecular docking studies propose the possible binding of TBA161 in a pocket adjacent to the catalytic site. This study shows that the zebrafish infection model is suitable for rapidly identifying promising scaffolds with in vivo activity.
On-demand Patterning for Organic Light-emitting Diodes Using Laser Irradiation
Authors: Sugimoto Ryota , Morimoto Masahiro , Naka Shigeki
Published: October 2021

We investigated the patterning of organic light-emitting diodes using a blue laser irradiation after making a uniform device. Laser patterning was carried out under ambient atmosphere after the organic layer was deposited. The laser irradiation part was quenched, and it was shown that optional patterning was possible. This technique is expected to be a fabrication technique for on-demand pattern emission.
Διατροφικές παρεμβάσεις στα ASD παιδιά Η περίπτωση της GFCF δίαιτας
Authors: Καραγιάννη Ελένη , Παπαδάκη Αγγελική
Published: October 2021

Ο αυτισμός αποτελεί μία σύνθετη νευροαναπτυξιακή διαταραχή, που οφείλεται σε εγκεφαλική δυσλειτουργία και εκδηλώνεται πρώιμα στην παιδική ηλικία. Τα τελευταία χρόνια, καθώς ολοένα και περισσότερες έρευνες εστιάζουν στην αλληλεπίδραση του μικροβιώματος του εντέρου με τη νευρολογική λειτουργία του εγκεφάλου, το ενδιαφέρον πλέον στρέφεται στους συσχετισμούς της παθοψυχολογίας του ASD με ζητήματα διατροφής. Σκοπός της έρευνας είναι να εξετάσει τη θετική επίδραση σύγχρονων διατροφικών προσεγγίσεων στην αντιμετώπιση των νευροψυχολογικών προβλημάτων των ASD παιδιών, αποβλέποντας στην ενδυνάμωση της λειτουργικότητας τους. Τα ευρήματα έδειξαν ότι τέτοιες διατροφικές στρατηγικές, όπως η GFCF δίαιτα, η κετογονική δίαιτα, η πρόσληψη κουρκουμίνης, το γάλα καμήλας και τα προβιοτικά, λειτουργούν ευεργετικά στην αντιμετώπιση των γαστρεντερικών διαταραχών και των τροφικών αλλεργιών, που επιτείνουν την εκδήλωση νευροσυμπεριφορικών συμπτωμάτων. Συμπερασματικά, προκύπτει ότι θεραπευτικές διατροφικές παρεμβάσεις, που βασίζονται στην επαρκή πρόσληψη θρεπτικών συστατικών, αποβλέποντας στη βέλτιστη ανάπτυξη των ASD παιδιών και λαμβάνουν χώρα υπό ιατρική παρακολούθηση και αξιολόγηση, δύνανται να βελτιώσουν την κλινική και κοινωνική εικόνα τους, εξασφαλίζοντάς τους καλύτερη ποιότητα ζωής.
Η μέθοδος της Αισθητηριακής ολοκλήρωσης σε παιδιά με Αυτισμό
Authors: Χατζηστυλιανού Βασιλική
Published: October 2021

Η σημερινή παρουσίαση εστιάζει στη μέθοδο της Αισθητηριακής Ολοκλήρωσης και στις τεχνικές παρέμβασης σε παιδιά με Αυτισμό. Ο όρος «αισθητηριακή ολοκλήρωση» άρχισε να χρησιμοποιείται τη δεκαετία του 1960,  όταν η Jean Ayres έγραψε τα πρώτα επιστημονικά άρθρα αναφερόμενη στον όρο αυτόν (James, 2011). Η Α.Ο. είναι «η ικανότητα του ατόμου να συνθέτει, να οργανώνει και να επεξεργάζεται τις εισερχόμενες αισθητηριακές πληροφορίες που λαμβάνει από το σώμα και το περιβάλλον, ώστε να παράγει στοχοκατευθυνόμενες αντιδράσεις», (Arkwright, 1998). Η ίδια τόνιζε τη σημασία της ΑΟ, καθώς και τα οφέλη που έχει σε ένα παιδί με Διάχυτες Αναπτυξιακές Διαταραχές.  Η μέθοδος στηρίζεται στο παιχνίδι και μέσα από αυτό, το παιδί προσλαμβάνει αισθητηριακά ερεθίσματα. Επιπλέον, αναπτύσσονται οι προσαρμοστικές αντιδράσεις, η ικανότητα επεξεργασίας και εκτέλεσης μίας δραστηριότητας, ο κινητικός σχεδιασμός, ο χρονισμός και η επίλυση προβλήματος (Ayres, 1972, Koomar & Bundy, 2002).  Οι ειδικοί άρχισαν να μελετούν τα συμπτώματα του Αυτισμού και έπειτα προέβησαν σε μια σειρά επιστημονικών ερευνών ώστε να εξακριβώσουν αν όντως η μέθοδος αυτή είναι αποτελεσματική. Τα παιδιά που συμμετείχαν στις έρευνες ήταν αγόρια και κορίτσια με ΔΑΦ, ηλικίας 3-12 ετών (Fombonne, 2003). Τα αποτελέσματα έδειξαν ότι υπήρξαν θετικές αλλαγές στην αισθητηριακή επεξεργασία, στις κοινωνικές δεξιότητες, στις Δραστηριότητες Καθημερινής Ζωής, στις κινητικές δεξιότητες και στο συναισθηματικό τομέα.  Κατέληξαν λοιπόν, ότι η μέθοδος δρα πολυαισθητηριακά και βοηθά στην ομαλή αυτορρύθμιση των αισθητηριακών συστημάτων του παιδιού με ΔΑΦ.
Giorgos Antoniou and A. Dirk Moses, eds., The Holocaust in Greece
Authors: Doxiadis Evdoxios
Published: October 2021

Review of Giorgos Antoniou and A. Dirk Moses, eds. The Holocaust in Greece.Cambridge: Cambridge University Press, 2018. xv + 378 pp.
Mathieu Grenet, La fabrique communautaire: Les Grecs à Venise, Livourne et Marseille, 1770–1840
Authors: Zanou Konstantina
Published: October 2021

Review of Mathieu Grenet. La fabrique communautaire: Les Grecs à Venise, Livourne et Marseille, 1770–1840. Athens: École française d’Athènes; Rome: École française de Rome and, 2016. 456 pp.
Dimitris Papanikolaou, Κάτι τρέχει με την οικογένεια: Έθνος, πόθος και συγγένεια την εποχή της κρίσης [There is something about the family: Nation, desire and kinship at a time of crisis]
Authors: Plantzos Dimitris
Published: October 2021

Review of Dimitris Papanikolaou. Κάτι τρέχει με την οικογένεια: Έθνος, πόθος και συγγένεια την εποχή της κρίσης [There is something about the family: Nation, desire and kinship at a time of crisis]. Athens: Patakis, 2018. 448 pp.
Case Report: Recurrent retinal vein occlusion as the first clinical manifestation of systemic lupus erythematosus in a male patient
Authors: Ben Brahim Marwa , Arfa Sondes , Boubaker Fadia , Chelly Jihen , Ammari Wafa , Hammami Sonia , Arbi Fatma , Berriche Olfa
Published: October 2021

Systemic lupus erythematosus (SLE) is a chronic, autoimmune disease characterized by widespread clinical manifestations and immunological disorders. A myriad of ocular manifestations can be seen in patients with SLE. The most vision-threatening complication is vaso-occlusive retinopathy including retinal vein occlusion (RVO). RVO associated with SLE is well described in the literature and its association with antiphospholipid antibodies is recognized. However, RVO as the initial manifestation of SLE is scarcely reported.

Herein, we report the first case of recurrent RVO as the revealing manifestation of SLE in a 40-year-old male patient. He had two consecutive episodes of decreased vision. Ophthalmologic examination disclosed a branch retinal vein occlusion the first time and a central retinal vein occlusion the second time. The diagnosis of SLE was established based on clinical and immunological criteria. He was prescribed antiplatelet therapy, hydroxychloroquine at 5.5 mg/kg/day, and intravitreal anti-vascular endothelial growth factor (VEGF) antibodies regimen. He slowly improved under treatment.
Learning outcomes of leader and leadership development: Method of Soft and Female leadership (SFL) empirical framework for driving the gender equality change in Mediterranean Engineering Education
Authors: Zabaniotou Anastasia
Published: October 2021

The foundation of gender equality was built some decades ago, but higher education institutions are far from achieving it. Perhaps the leadership needs to integrate new narratives for a greater commitment especially in engineering, and new tools for the existing toolbox. This study aims to share the outcomes of soft female leadership framework (SFL) development for gender equality at the RMEI network, entailing the commitment of top-managers from engineering schools, creation of new leaders to lead the change at their institutions, students acting as change-agents, and an active community of practice. The SFL toolbox comprises self-awareness, humanistic care, intuition, creativity, and trust. The transformation of mindset, skillset, and culture entails using Sustainable Development Goals (SDGs), ‘Systemic View of Life’ arguments, and drawing knowledge from organizational learning frameworks, scientific phenomena, and mechanisms, such as a) 4I-Intuiting-Interpreting-Integrating-Institutionalizing organizational learning process starting from intuition to achieve an institutional change; b) ‘Stigmergy’ scientific mechanism of self-organized collective schemes with coordinated actions and interactions, in which the action performed by an agent leaves a trace in the environment that stimulates subsequent actions; c) ‘Spillover’ phenomenon advocating that the behavior of an agent can bring the adoption of related behaviors by other agents. The RMEI gender equality plan (GEP) was evaluated by the HORIZON2020 TARGET project consortium. The SFL excelled as successful in setting goals, articulating a policy that integrates systems approach frameworks, insights from science and technology, innovation, ecology, philosophy, self-awareness, ethics, and values. The Covid-19 pandemic disrupted physical meetings, but the process of change was not ceased at the network because we disrupted the disruption by boosting collaborative knowledge, consolidation and dissemination processes. The SFL framework integrates context, regional, and temporal characteristics, alongside cognitive, affective, and motivational outcomes over behavioral outcomes, new mindsets beyond organizational skills, and collaborative learning over individual learning.
Mission-based optimal morphing parameters for rotors with combined chord and twist morphing
Authors: Majeti Rohin Kumar , Benz Stephan
Published: October 2021

Background: The fixed geometry rotor blades in today’s helicopters do not give the best performance throughout the duration of any mission. However, low-speed and high-speed flights have different geometrical requirements for the shape of the most efficient rotor blades. With advancements in morphing technologies, these can be applied to change the shape of the blades in different flight regimes.

Methods: Two different helicopter rotor morphing concepts – namely, the linearly variable chord extension and the torque-tube based twist - under the framework of the European project SABRE were investigated for their optimal geometric parameters using a Particle Swarm Optimization (PSO) algorithm. Since the morphing parameters were dependent on the mission profile, three different missions representing typical helicopter applications were chosen. The optimization problem was posed both as single objective (power) and as multi-objective (power, tip elastic torsion and vibratory hub load). Based on the insights drawn from these investigations, a rotor was set up including both morphing concepts in a single blade.

Results: The rotor with combined chord and twist morphing was shown to have better performance than the baseline blade, while keeping the penalty on the elastic torsion and vibration of the rotor to a minimum.

Conclusions: Chord and twist are both important parameters determining the efficiency of a rotor blade. Since they have non-overlapping requirements, combining the two morphing concepts into a single blade can yield higher performance than the individual ones.
Identifying and characterising Thrap3, Bclaf1 and Erh interactions using cross-linking mass spectrometry
Authors: Shcherbakova Liudmila , Pardo Mercedes , Roumeliotis Theodoros , Choudhary Jyoti
Published: October 2021

Background: Cross-linking mass spectrometry (XL-MS) is a powerful technology capable of yielding structural insights across the complex cellular protein interaction network. However, up to date most of the studies utilising XL-MS to characterise individual protein complexes’ topology have been carried out on over-expressed or recombinant proteins, which might not accurately represent native cellular conditions.

Methods: We performed XL-MS using MS-cleavable crosslinker disuccinimidyl sulfoxide (DSSO) after immunoprecipitation of endogenous BRG/Brahma-associated factors (BAF) complex and co-purifying proteins. Data are available via ProteomeXchange with identifier PXD027611.

Results: Although we did not detect the expected enrichment of crosslinks within the BAF complex, we identified numerous crosslinks between three co-purifying proteins, namely Thrap3, Bclaf1 and Erh. Thrap3 and Bclaf1 are mostly disordered proteins for which no 3D structure is available. The XL data allowed us to map interaction surfaces on these proteins, which overlap with the non-disordered portions of both proteins. The identified XLs are in agreement with homology-modelled structures suggesting that the interaction surfaces are globular.

Conclusions: Our data shows that MS-cleavable crosslinker DSSO can be used to characterise in detail the topology and interaction surfaces of endogenous protein complexes without the need for overexpression. We demonstrate that Bclaf1, Erh and Thrap3 interact closely with each other, suggesting they might form a novel complex, hereby referred to as BET complex. This data can be exploited for modelling protein-protein docking to characterise the three-dimensional structure of the complex. Endogenous XL-MS might be challenging due to crosslinker accessibility, protein complex abundance or isolation efficiency, and require further optimisation for some complexes like the BAF complex to detect a substantial number of crosslinks.
The genome sequence of the Australian filarial nematode, Cercopithifilaria johnstoni
Authors: McCann Kirsty , Grant Warwick , Doyle Stephen R.
Published: October 2021

We present a genome assembly and annotation of an individual femaleCercopithifilaria johnstoni, a parasitic filarial nematode that is transmitted by hard ticks (Ixodidae) to infect a broad range of native Australian murid and marsupial hosts. The genome sequence is 76.9 Mbp in length, and although in draft form (N50 = 99 kbp, N50[n] = 232), is largely complete based on universally conserved orthologs (BUSCOs; genome = 94.9%, protein = 96.5%) and relative to other related filarial species. These data represent the first genomic resources for the genusCercopithifilaria, a group of parasites with a broad host range, and form the basis for comparative analysis with the human-infective parasite,Onchocerca volvulus, both of which are responsible for similar eye and skin pathologies in their respective hosts.