Miracle-dz/UniFAR-FTUs huggingface dataset:
Reconstitution of renal cyst formation in 3D culture reveals a role for AMOT and Yap1 in determining cyst size

Despite substantial progress in identifying and understanding causative mutations in autosomal dominant polycystic kidney disease (ADPKD), little is known about subsequent cellular events leading to cyst formation. In prior studies we reported that Cadherin 8, a type II Cadherin, expression is sufficient to induce cyst emergence from HK-2 cells grown as tubule arrays in collagen matrix (1). However, emergent cysts did not exhibit the luminal enlargement observed in ADPKD. In this communication, we reconstitute cyst emergence with consequent cyst lumen expansion in 3D culture by stable co-expression of Cadherin 8 in combination with a constitutively active mutant of YAP1, the key effector of the HIPPO pathway. Specifically, immortalized cells derived from ADPKD cyst epithelia formed cysts with substantially larger lumen sizes when transduced with YAP1-5SA. Conversely, expression of the YAP1 inhibitor, AMOTL1, in these cells resulted in their forming cysts with smaller lumens than control cells. Our data show that cyst formation results from a sequential two-step process consisting of cyst initiation and subsequent cyst expansion. Taken together, cyst initiation induced by Cadherin 8 expression is proposed to result from decreased cell-cell adhesion while cyst expansion is driven by increased Yap1 activity.
Fine-scale survey of intertidal macroalgae reveals recent changes in a cold-water biogeographic stronghold

Global warming has been causing severe impacts on marine ecosystems, a notorious one being shifts in the geographical ranges of species. The north-western coast of the Iberian Peninsula is an especially interesting zone to study distributional shifts as it has a strong latitudinal thermal gradient, is influenced by the Canary upwelling system (which partially cancels coastal warming) and holds some of the most diverse macroalgae communities in Europe. Notably, it is within this region that many cold-water species, common in northern Europe, have their southernmost distribution refuge. Recent studies hypothesize that the environmental conditions may be nonetheless changing and already threatening this biodiversity hotspot. The main goal of this study was to carry out a fine-scale assessment of the distributional limits of several macroalgae in North-western Iberia, as well as identify possible population and range shifts using historical data (2001-2005) as reference. In addition, invasive species were also surveyed. We also assessed if the regions of (i) Galicia, (ii) Northern Portugal, and (iii) Central Portugal displayed distinctive characters regarding macroalgae composition and abundance. We identified an increase in abundance of some invasive macroalgae as well as a decrease in the abundance of some cold-water species. In the most severe cases, cold-water species were extirpated along hundreds of km. The compounded effect of the decrease in the abundance of cold-water species and the increase in the abundance of invasive species is leading to the homogenization of macroalgae communities in north-western Iberia.
Increased core body temperature exacerbates defective protein prenylation in mouse models of mevalonate kinase deficiency

Mevalonate kinase deficiency (MKD) is caused by biallelic loss-of-function mutations in MVK, leading to recurrent fevers and systemic inflammation. We describe new mouse avatars of MKD bearing p.Val377Ile (the commonest variant) or deletions in Mvk. Compound heterozygous mice recapitulated the biochemical phenotype of MKD, with build-up of unprenylated GTPases and increased plasma mevalonic acid. Mice with different deficiencies in mevalonate kinase revealed new insights into the genotype-phenotype relationship and mirrored the variability in the prenylation defect in human MKD, with p.V377I homozygous mice having a milder phenotype than compound heterozygous animals. The inflammatory response to LPS was enhanced in compound heterozygous mice in vivo and elevated serum interleukin-1β was abrogated by NLRP3 inflammasome inhibition. Increased temperature dramatically but reversibly exacerbated the deficit in the mevalonate pathway and defective prenylation in vitro and in vivo, highlighting increased body temperature as a likely trigger of inflammatory flares and an additional potential target for future therapeutic approaches.
A BALB/c IGHV Reference Set, Defined by Haplotype Analysis of Long-Read VDJ-C Sequences From F1 (BALB/c x C57BL/6) Mice

The immunoglobulin genes of inbred mouse strains that are commonly used in models of antibody-mediated human diseases are poorly characterized. This compromises data analysis. To infer the immunoglobulin genes of BALB/c mice, we used long-read SMRT sequencing to amplify VDJ-C sequences from F1 (BALB/c x C57BL/6) hybrid animals. Previously unreported strain variations were identified in the Ighm and Ighg2b genes, and analysis of VDJ rearrangements led to the inference of 278 germline IGHV alleles. 169 alleles are not present in the C57BL/6 genome reference sequence. To establish a set of expressed BALB/c IGHV germline gene sequences, we computationally retrieved IGHV haplotypes from the IgM dataset. Haplotyping led to the confirmation of 162 BALB/c IGHV gene sequences. A musIGHV398 pseudogene variant also appears to be present in the BALB/cByJ substrain, while a functional musIGHV398 gene is highly expressed in the BALB/cJ substrain. Only four of the BALB/c alleles were also observed in the C57BL/6 haplotype. The full set of inferred BALB/c sequences has been used to establish a BALB/c IGHV reference set, hosted at https://ogrdb.airr-community.org. We assessed whether assemblies from the Mouse Genome Project (MGP) are suitable for the determination of the genes of the IGH loci. Only 37 (43.5%) of the 85 confirmed IMGT-named BALB/c IGHV and 33 (42.9%) of the 77 confirmed non-IMGT IGHV were found in a search of the MGP BALB/cJ genome assembly. This suggests that Adaptive Immune Receptor Repertoire sequencing (AIRR-Seq) data, but not currently-available genome assemblies, are suited to the documentation of germline IGHV genes.
Rate-distortion theory of neural coding and its implications for working memory

Rate-distortion theory provides a powerful framework for understanding the nature of human memory by formalizing the relationship between information rate (the average number of bits per stimulus transmitted across the memory channel) and distortion (the cost of memory errors). Here we show how this abstract computational-level framework can be realized by a model of neural population coding. The model reproduces key regularities of visual working memory, including some that were not previously explained by population coding models. We verify a novel prediction of the model by reanalyzing recordings of monkey prefrontal neurons during an oculomotor delayed response task.
Metabolome and transcriptome analysis reveals components regulating triterpenoid saponin biosynthesis of soapberry

Soapberry (Sapindus mukorossi Gaertn.) pericarps are rich in valuable bioactive triterpenoid saponins. However, the saponin content dynamics and the molecular regulatory network of saponin biosynthesis in soapberry pericarps remain largely unclear. Here, we performed combined metabolite profiling and transcriptome analysis to identify saponin accumulation kinetic patterns, investigate gene networks, and characterize key candidate genes and transcription factors involved in saponin biosynthesis in soapberry pericarps. A total of 54 saponins were tentatively identified, including 25 that were differentially accumulated. Furthermore, 49 genes putatively involved in sapogenin backbone biosynthesis and some candidate genes assumed to be responsible for the backbone modification, including 41 cytochrome P450s and 45 glycosyltransferases, were identified. Saponin-specific clusters/modules were identified by Mfuzz clustering and weighted gene co-expression network analysis, and one TF–gene regulatory network underlying saponin biosynthesis was proposed. The results of yeast one-hybrid assay and electrophoretic mobility shift assay suggested that SmbHLH2, SmTCP4, and SmWRKY27 may play important roles in the triterpenoid saponin biosynthesis by directly regulating the transcription of SmCYP71D-3 in soapberry pericarp. Overall, these findings provide valuable information for understanding the molecular regulatory mechanism of saponin biosynthesis, enriching the gene resources, and guiding further research on triterpenoid saponin accumulation in soapberry pericarps. One–sentence summary Combining metabolome and transcriptome analysis to identify saponin kinetic patterns, gene networks, and key candidate genes and transcription factors involved in saponin biosynthesis of soapberry.
Customer knowledge and behavior on the use of food refrigerated display cabinets: A Portuguese case

Abstract This article presents a study on customer knowledge and habits regarding the use of refrigerated display cabinets (RDC). The study was carried out on a sample of Portuguese retail stores’ customers, using a questionnaire survey available through an Internet platform. The sample consisted of 136 individuals, who voluntarily participated in the study. Questions included the characterization of the sociodemographic population involved. The questionnaire included different questions to related with RDC, namely customer knowledge about the appearance of each RDC equipment, questions to evaluate the respondents’ perception about the advantages and disadvantages related to open or glass-door closed RDC, questions to assess the participants’ habits and behavior when purchasing food products from glass-door closed RDC (frequency and duration of door open), questions to characterize the consumers’ habits on purchasing food products from RDC, and also questions to characterize the consumers’ shopping attitudes in the context of the COVID-19 pandemic, caused by SARS-CoV-2. The results seem to indicate that customers prefer closed RDC; for example, 61.8% of participants prefer products preserved in glass-door closed RDC, against 6.6% that admit to preferring products preserved in open RDC. Therefore, we can deduce that the existence of doors does not appear to be an obstacle to purchasing food products. Regarding the use of glass-door closed RDC, 80.1% of the participants say they just open the door once, and 53.7% of the costumers believe they keep the door open in the interval [4‒6 s]. This indicates that Portuguese customers are quite well informed about food safety issues and seem to follow assertive attitudes when purchasing food products from RDC. This study reinforces the benefits of replacing open RDC by closed glass-doors allowing significant energy savings.
Parameterization of long-period eclipsing binaries

Abstract One of the important sources for independent determination of stellar masses is eclipsing binaries with components on the main sequence, and with observable spectral lines of both components. The parameters of such stars are used to construct the mass–luminosity relation for stars of high and intermediate masses. Among them, the type of long-period eclipsing binaries stands out, the parameters of which are currently not fully determined, which is associated with the difficulties caused by the need for long-term observations. In this article, we will review the currently available observational data for such objects and discuss the prospects for their use to determine stellar masses.
Study of plant resources with ethnomedicinal relevance from district Bagh, Azad Jammu and Kashmir, Pakistan

Abstract An ethnomedicinal expedition was conducted to collect and record indigenous knowledge about the use of medicinal plants by local inhabitants of four villages (Chittra, Topi, Pandi, and Kalri) of district Bagh, Azad Jammu and Kashmir. Ethnomedicinal data were obtained from 60 randomly selected local inhabitants of the study area through semi-structured questionnaires and interviews. These data were analyzed quantitatively through different ethnobotanical indices including family importance value, relative frequency of citation, use value (UV), fidelity level (FL), informant consensus factor (ICF), and Jaccard index (JI). our study reported 69 medicinal plants belonging to 39 families. Rosaceae (9 species) was a dominant family of the study area. Herb (54.83%) was dominant growth form of plants used for medicinal purpose. Leaves contributed maximum usage (44.29%) for curing diseases. Decoction (23 records) was most used mode of utilization. Relative frequency of citation and UV ranged from 0.03–0.85 and 0.05–1.17, respectively. There were 4 plant species with 100% FL. Highest ICF (0.88%) was found for gastrointestinal diseases. By comparing results with previous study, JI ranged from 0.54 to 24.43%. Our results found that there were 18 plant species not reported with ethnomedicinal aspect in previous studies from district Bagh region. The research of this study concludes that the area is rich with medicinal plants and the local inhabitant of this area still prefer medicinal plants over allopathic medicines for treating different ailments. Comparative analysis has shown some novel uses of plant species which may be due to cultural differences of the study area. However, awareness and pharmacological study are needed to conserve and unveil pharmaceutically important plants.
Key competences for Transport 4.0 – Educators’ and Practitioners’ opinions

Abstract This study deals with the subject of the Fourth Industrial Revolution; that is, Industry 4.0 or Revolution 4.0 discusses its impact on contemporary road transport and the development of Transport 4.0. The needs of the industry as well as the transport industry change diametrically with the correspondingly sudden and rapid development of technology, as well as the requirements of companies hiring new employees. To meet the future requirements of Revolution 4.0, the vocational training program should undergo a major overhaul. Therefore, it is important to determine what skills and qualifications of employees of transport companies should be currently developed. The study presents fragments of analyses performed as part of the F2J – “Future-Ready Ed Right Skills To Right Job” project, financed by the European Commission under the Erasmus + Program. The main goal of this article is to identify the skills and characteristics of transport companies’ employees that are most required from the point of view of the Revolution 4.0. Both technical and soft skills to be imparted into the human workforce for Transport 4.0 were reported. Study shows the need to address the integration of the concept of Revolution 4.0 into the current education system. The article is based on the analysis of data from highly qualified employees who work in transport companies (practitioners), as well as people involved in education and comprehensive preparation of people for work in the transport industry (educators). A total of 63 people participated in the study.
Cooling of High-Performance Server Modules Using Direct Immersion

An alternative to air-cooling of high performance computing equipment is presented. Heat removal via pool boiling in FC-72 was tested. Tests were conducted on a multichip module using 1.8 cm × 1.8 cm test die with multiple thermal test cells with temperature sensing capability. Measurements with the bare silicon die in direct contact with the fluid are reported. Additional testing included the test die directly indium-attached to copper heat spreaders having surface treatments. A screen-printed sintered boiling-enhanced surface (4 cm × 4 cm) was evaluated. Tests were conducted on an array of five die. Parameters tested include heat flux levels, dielectric liquid pool conditions (saturated or subcooled), and effect of neighboring die. Information was gathered on surface temperatures for a range of heat flux values up to 12 W/cm2. The highest heat dissipated from a circuit board with five bare die was 195 W (39 W per die). Addition of the heat spreader allowed heat dissipation of up to 740 W (from a five-die array). High-speed imaging was also acquired to help examine detailed information on the boiling process. Numerical modeling indicated that placing multiple boards in close proximity to each other did not degrade performance until board spacing was reduced to 3 mm. © 2012 ASME
A comprehensive public open space categorization using classification system for sustainable development of public open spaces

Our quality of life significantly depends on open spaces. They offer facility provision for a wide range of social interactions and provide habitats for flora and fauna. A classification of spaces would be useful in preparing public open space policies and fulfilling structure plan. This study aims to propose a comprehensive open space categorization using classification system for Malaysia. A deep investigation in sources in Malaysia reveals that there is lack of comprehensive classification of open spaces and just a hierarchy of open spaces presented. A critical literature review were carried out for this study to understand the approaches of this comprehensive classification and adapted them according to Malaysia context. In order to come up with a comprehensive classification in Malaysia, an analysis of comparison between several cities in different countries was done. The outcomes of the study will provide a systematic classification use for planner and policy makers in preparing open space strategies and in setting development plan policies. It is also useful for designers to obtain the best possible conceptual ideas when designing open spaces.
Integration of the Salmonella Typhimurium Methylome and Transcriptome Reveals That DNA Methylation and Transcriptional Regulation Are Largely Decoupled under Virulence-Related Conditions

While recent breakthroughs have enabled intense study of bacterial DNA modifications, limitations in current work have potentiated a surprisingly untested narrative that DNA methylation is a common mechanism of the bacterial response to environmental conditions. Essentially, whether epigenetic regulation of bacterial transcription is a common, generalizable phenomenon is a critical unanswered question that we address here. ABSTRACT Despite being in a golden age of bacterial epigenomics, little work has systematically examined the plasticity and functional impacts of the bacterial DNA methylome. Here, we leveraged single-molecule, real-time sequencing (SMRT-seq) to examine the m6A DNA methylome of two Salmonella enterica serovar Typhimurium strains: 14028s and a ΔmetJ mutant with derepressed methionine metabolism, grown in Luria broth or medium that simulates the intracellular environment. We found that the methylome is remarkably static: >95% of adenosine bases retain their methylation status across conditions. Integration of methylation with transcriptomic data revealed limited correlation between changes in methylation and gene expression. Further, examination of the transcriptome in ΔyhdJ bacteria lacking the m6A methylase with the most dynamic methylation pattern in our data set revealed little evidence of YhdJ-mediated gene regulation. Curiously, despite G(m6A)TC motifs being particularly resistant to change across conditions, incorporating dam mutants into our analyses revealed two examples where changes in methylation and transcription may be linked across conditions. This includes the novel finding that the ΔmetJ motility defect may be partially driven by hypermethylation of the chemotaxis gene tsr. Together, these data redefine the S. Typhimurium epigenome as a highly stable system that has rare but important roles in transcriptional regulation. Incorporating these lessons into future studies will be critical as we progress through the epigenomic era. IMPORTANCE While recent breakthroughs have enabled intense study of bacterial DNA modifications, limitations in current work have potentiated a surprisingly untested narrative that DNA methylation is a common mechanism of the bacterial response to environmental conditions. Essentially, whether epigenetic regulation of bacterial transcription is a common, generalizable phenomenon is a critical unanswered question that we address here. We found that most DNA methylation is static in Salmonella enterica serovar Typhimurium, even when the bacteria are grown under dramatically different conditions that cause broad changes in the transcriptome. Further, even when the methylation of individual bases change, these changes generally do not correlate with changes in gene expression. Finally, we demonstrate methods by which data can be stratified in order to identify coupled changes in methylation and gene expression.
IL-21 signaling promotes the establishment of KSHV infection in human tonsil lymphocytes by increasing early targeting of plasma cells

Factors influencing Kaposi’s sarcoma-associated herpesvirus (KSHV) transmission and the early stages of KSHV infection in the human immune system remain poorly characterized. KSHV is known to extensively manipulate the host immune system and the cytokine milieu, and cytokines are known to influence the progression of KSHV-associated diseases. Here, using our unique model of KSHV infection in tonsil lymphocytes, we investigate the influence of host cytokines on the establishment of KSHV infection in human B cells. Our data demonstrate that KSHV manipulates the host cytokine microenvironment during early infection and susceptibility is generally associated with downregulation of multiple cytokines. However, we show that IL-21 signaling promotes KSHV infection by promoting both plasma cell numbers and increasing KSHV infection in plasma cells as early as 3 days post-infection. Our data reveal that this phenotype is dependent upon a specific milieu of T cells, that includes IL-21 producing Th17, Tc17 and CD8+ central memory T cells. These results suggest that IL-21 plays a significant role in the early stages of KSHV infection in the human immune system and that specific immunological states favor the initial establishment of KSHV infection by increasing infection in plasma cells.
DB120406 977..986

Indians Identifies a New Susceptibility Locus at 2q21 Rubina Tabassum, Ganesh Chauhan, Om Prakash Dwivedi, Anubha Mahajan, Alok Jaiswal, Ismeet Kaur, Khushdeep Bandesh, Tejbir Singh, Benan John Mathai, Yogesh Pandey, Manickam Chidambaram, Amitabh Sharma, Sreenivas Chavali, Shantanu Sengupta, Lakshmi Ramakrishnan, Pradeep Venkatesh, Sanjay K. Aggarwal, Saurabh Ghosh, Dorairaj Prabhakaran, Reddy K. Srinath, Madhukar Saxena, Monisha Banerjee, Sandeep Mathur, Anil Bhansali, Viral N. Shah, Sri Venkata Madhu, Raman K. Marwaha, Analabha Basu, Vinod Scaria, Mark I. McCarthy, DIAGRAM,* INDICO,* Radha Venkatesan, Viswanathan Mohan, Nikhil Tandon, and Dwaipayan Bharadwaj
Hematological and toxicological parameters after metformin treatment during pancreatic carcinogenesis

Pancreatic cancer is the fourth-highest cancer killer among both men and women worldwide. In Egypt, pancreatic cancer incidence and mortality rates has been increasing in the last few years due to unknown reasons. The biguanides metformin is the most widely used first-line therapy for type 2 diabetes (T2D). Numerous observational studies have supported a protective role for metformin against a variety of cancer types as breast, liver and prostate cancer. This study aimed to investigate the anti-tumor effects of metformin treatment against pancreatic cancer induced in Syrian golden hamsters.by subcutaneous injection of A/nitrosobis (2-oxopropyl) amine (BOP). Gemcitabine was used as a conventional drug used for treatment of pancreatic cancer. The results show that metformin has no toxic effect against chemically induced pancreatic carcinogenesis of hamsters caused by BOP induction. Article history: Received: April 21, 2019 Revised: May 5, 2019 Accepted: Aug 18, 2019 Correspondence to: Dr. Elsayed I. Salim Ph.D., D. Med. Sc. Zoology Department, Faculty of Science, Tanta University, Egypt Tel : +201220177760 E-Mail: elsayed.salim@science.tanta,edu.eg