bluuebunny/crossref_metadata_2025 huggingface dataset:
Plant attributes interact with fungal pathogens and nitrogen addition to drive soil enzymatic activities and their temporal variation
Authors: Nwe Thu Zar , Maaroufi Nadia I. , Allan Eric , Soliveres Santiago , Kempel Anne
Published: October 2022

Nitrogen enrichment can alter soil communities and their functioning directly, via changes in nutrient availability and stoichiometry, or indirectly, by changing plant communities or higher trophic levels. In addition, soil biota and their associated functions may show strong temporal changes in their response to environmental changes, yet most current studies have only focused on one of these potential drivers or have measured soil functioning only once during the peak growing season. Therefore, we know little about the relative importance of the different mechanisms by which nitrogen enrichment affects soil communities, functioning and temporal stability.

In a large grassland experiment manipulating nitrogen enrichment, plant species richness, functional composition and foliar pathogen presence, we measured activities of two enzymes, β-glucosidase and acid phosphatase, as indicators of soil functioning. We did so across different seasons and years to assess their temporal dynamics and how consistently they responded to multiple drivers.

Nitrogen addition was the most important driver of β-glucosidase activity, and it increased β-glucosidase activity over time. However, interactions between plant attributes and fungicide application were the main drivers of acid phosphatase activity. The temporal stability of soil enzyme activity was differently affected by two facets of plant diversity (species richness [+] and functional diversity [-]), with nitrogen and fungicide addition dampening these effects.

Synthesis: Fungicide effects, and their interactions with plant diversity, show the importance of foliar pathogens not only for above-but also for belowground processes, and highlight the possibility that these plant enemies are major modulators in the relationships between plant diversity and ecosystem functioning. We also show the need to consider temporal dynamics in belowground processes to better understand the responses of ecosystem functioning to environmental changes such as nutrient enrichment.
More than half of the variance inin-vivo1H-MRS metabolite estimates is common to all metabolites
Authors: Prisciandaro James J. , Zöllner Helge J. , Murali-Manohar Saipavitra , Oeltzschner Georg , Edden Richard A. E.
Published: October 2022

The present study characterized associations among brain metabolite levels, applying bivariate and multivariate (i.e., factor analysis) statistical methods to tCr-referenced estimates of the major PRESS1H-MRS metabolites (i.e., tNAA/tCr, tCho/tCr, mI/tCr, Glx/tCr), acquired from medial parietal lobe in a large (n=299), well-characterized international cohort of healthy volunteers (Povazan et al., 2020). Results supported the hypothesis that1H-MRS-measured metabolite estimates are moderately intercorrelated (Mr= 0.42,SDr= 0.11,ps < 0.001), with more than half (i.e., 57%) of the total variability in metabolite estimates common to (i.e., shared by) all metabolites. Older age was significantly associated with lower levels of common metabolite variance (CMV;β= -0.09,p= 0.048), despitenotbeing associated with levels of any individual metabolite. Holding CMV levels constant, females had significantly lower levels of total choline (i.e., unique metabolite variance or UMV;β= -0.19,p< 0.001), mirroring significant bivariate correlations between sex and total choline reported previously. If replicated, these results would suggest that applied1H-MRS researchers should shift their analytical framework from examining bivariate associations between individual metabolites and specialty-dependent (e.g., clinical, research) variables of interest (e.g., using t-tests) to examining multi-variable (i.e., covariate) associations between multiple metabolites and specialty-dependent variables of interest (e.g., using multiple regression). Without this shift, clear interpretation of associations of1H-MRS metabolites with specialty-dependent variables of interest may not be possible.
Changes in lung sialidases in male and female mice after bleomycin aspiration
Authors: Pilling Darrell , Sahlberg Kyle , Chen Wensheng , Gomer Richard H.
Published: October 2022

Aim of the study

Sialidases, also called neuraminidases, are enzymes that cleave terminal sialic acids from glycoconjugates. In humans and mice, lung fibrosis is associated with desialylation of glycoconjugates and upregulation of sialidases. There are four mammalian sialidases, and it is unclear when the four mammalian sialidases are elevated over the course of inflammatory and fibrotic responses, whether tissue resident and inflammatory cells express different sialidases, and if sialidases are differentially expressed in male and females.

Materials and Methods

To determine the time course of sialidase expression and the identity of sialidase expressing cells, we used the bleomycin model of pulmonary fibrosis in mice to examine levels of sialidases during inflammation (days 3 - 10) and fibrosis (days 10 - 21).

Results

Bleomycin aspiration increased sialidase NEU1 at days 14 and 21 in male mice and day 10 in female mice. NEU2 levels increased at day 7 in male and day 10 in female mice. NEU3 appears to have a biphasic response in male mice with increased levels at day 7 and then at days 14 and 21, whereas in female mice NEU3 levels increased over 21 days. In control mice, the sialidases were mainly expressed by EpCAM positive epithelial cells, but after bleomycin, epithelial cells, CD45 positive immune cells, and alveolar cells expressed NEU1, NEU2, and NEU3. Sialidase expression was higher in male compared to female mice. There was little expression of NEU4 in murine lung tissue.

Conclusions

These results suggest that sialidases are dynamically expressed following bleomycin, that sialidases are differentially expressed in male and females, and that of the four sialidases only NEU3 upregulation is associated with fibrosis in both male and female mice.
Trends in Subcutaneous Tumour Height and Impact on Measurement Accuracy
Authors: Brough Daniel , Amos Hope , Turley Karl , Murkin Jake
Published: October 2022

Tumour volume is typically calculated using only length and width measurements, using width as a proxy for height in a 1:1 ratio. When tracking tumour growth over time, important morphological information and measurement accuracy is lost by ignoring height, which we show is a unique variable. Lengths, widths, and heights of 9,522 subcutaneous tumours in mice were measured using 3D and thermal imaging. The average width:height ratio was found to be 1:3 proving that using width as a proxy for height overestimates tumour volume. Comparing volumes calculated with and without tumour height to the true volumes of excised tumours indeed showed that using the volume formula including height produced volumes 36X more accurate. Monitoring the width:height relationship (prominence) across tumour growth curves indicated that prominence varied, and that height could change independent of width. Twelve cell lines were investigated individually; the scale of tumour prominence was cell line-dependent with relatively less prominent tumours (MC38, BL2, LL/2) and more prominent tumours (RENCA, HCT116) detected. Prominence trends across the growth cycle were also dependent on cell line; prominence was correlated with tumour growth in some cell lines (4T1, CT26, LNCaP), but not others (MC38, TC-1, LL/2). When pooled, invasive cell lines produced tumours that were significantly less prominent at volumes >1200mm3 compared to non-invasive cell lines (P<0.001). Modelling was used to show the impact of the increased accuracy gained by including height in volume calculations on several efficacy study outcomes. Variations in accuracy contribute to experimental variation and irreproducibility of data, therefore we strongly advise researchers to measure height to improve accuracy in tumour studies.
Regulation of chromatin microphase separation by adsorbed protein complexes
Authors: Adame-Arana Omar , Bajpai Gaurav , Lorber Dana , Volk Talila , Safran Samuel A.
Published: October 2022

We show evidence of the association of RNA Polymerase II (RNAP) with chromatin in a core-shell organization, reminiscent of microphase separation where the cores comprise dense chromatin and the shell, RNAP and chromatin with low density. These observations motivate our physical model for the regulation of core-shell chromatin organization. Here, we model chromatin as a multiblock copolymer, comprising active and inactive regions (blocks) that are both in poor solvent and tend to be condensed in the absence of binding proteins. However, we show that the solvent quality for the active regions of chromatin can be regulated by the binding of protein complexes (e.g. RNAP). Using the theory of polymer brushes, we find that such binding leads to swelling of the active chromatin regions which in turn, modifies the spatial organization of the inactive regions. In addition, we use simulations to study spherical chromatin micelles, whose cores comprise inactive regions and shells comprise active regions and bound protein complexes. In spherical micelles the swelling increases the number of inactive cores and controls their size. Thus, genetic modifications affecting the binding strength of chromatin-binding protein complexes may modulate the solvent quality experienced by chromatin and regulate the physical organization of the genome.
ATM-Mediated Double-Strand Break Repair Is Required for Meiotic Genome Stability at High Temperature
Authors: Zhao Jiayi , Gui Xin , Ren Ziming , Fu Huiqi , Yang Chao , Liu Qingpei , Zhang Min , Wang Wenyi , Wang Chong , Schnittger Arp , Liu Bing
Published: October 2022

In eukaryotes, the conserved kinase Ataxia Telangiectasia Mutated (ATM) negatively regulates DNA double-strand break (DSB) formation and plays a central role in DSB repair. Here, by using cytogenetic approaches, we demonstrate that ATM also plays an essential role in protecting meiotic chromosome integrity in Arabidopsis thaliana at extreme high temperature. We determined the chromosome localization patterns of DSB formation proteins SPO11-1 and DFO during prophase I, both of which were disturbed by heat stress. Evaluation of the number of RAD51, DMC1, SPO11-1 and DFO protein foci in meiocytes of Arabidopsis atm mutant clarifies that ATM does not mediate the heat-induced reduction in DSB formation. Interestingly, meiotic spread analysis showed that chromosome fragmentation level was significantly increased in atm but was lowered in the mre11 and mre11 atm mutants under high temperature, indicating that ATM-dependent meiotic chromosome integrity at high temperature relies on the functional MRE1-RAD50-NBS1 (MRN) complex. Moreover, contrary to the rad51 and mnd1 mutants, which exhibited enhanced meiotic chromosome integrity under heat stress, the rad51 atm and mnd1 atm mutants retained high levels of chromosome fragmentation at extreme high temperature. Furthermore, heat stress reduced chromosome fragmentation level in the syn1 and syn1 atm mutants. Collectively, these data suggest that ATM-mediated DSB repair is required for meiotic genome stability in plants at extreme high temperature, which possibly acts in a RAD51-independent manner and relies on functional chromosome axis.
Single cell evaluation of endocardial HAND2 gene regulatory networks reveals critical HAND2 dependent pathways impacting cardiac morphogenesis
Authors: George Rajani M , Firulli Beth A , Podicheti Ram , Rusch Douglas B , Mannion Brandon J , Pennacchio Len A , Osterwalder Marco , Firulli Anthony B
Published: October 2022

The transcription factor HAND2 plays critical roles during cardiogenesis. Hand2 endocardial deletion (H2CKO) results in tricuspid atresia or double inlet left ventricle with accompanying intraventricular septum defects, hypo-trabeculated ventricles, and an increased density of coronary lumens. To understand the regulatory mechanisms of these phenotypes, single cell transcriptome analysis of E11.5 H2CKO hearts was performed revealing a number of disrupted endocardial regulatory pathways. Utilizing HAND2 DNA occupancy data, we identify several HAND2-dependent enhancers, including two endothelial enhancers for the sheer-stress master regulator, KLF2. A 1.8kb enhancer located 50kb upstream of the Klf2 transcriptional start site imparts specific endothelial/endocardial expression within the vasculature and endocardium. This enhancer is HAND2-dependent for ventricular endocardium expression but HAND2-independent for Klf2 vascular and valve expression. Deletion of this Klf2 enhancer reveals reduced Klf2 expression within ventricular endocardium. These data reveal that HAND2 functions within endocardial gene regulatory networks including sheer stress response.
Harmonic memory signals in the human cerebral cortex induced by sematic relatedness of words
Authors: Noguchi Yasuki
Published: October 2022

When we memorize multiple words simultaneously, semantic relatedness among those words assists memory. For example, the information of “apple”, “banana” and “orange” will be connected via a common concept of “fruits” and become easy to retain and recall. Neural mechanisms underlying this semantic integration in verbal working memory remain unclear. Here I used electroencephalography (EEG) and investigated neural signals when healthy human participants memorized five nouns semantically related (Sem trial) or not (NonSem trial). The regularity of oscillatory signals (8 – 30 Hz) during the retention period was found to be lower in NonSem than Sem trials, indicating that memorizing words unrelated to each other induced a non-harmonic (irregular) waveform in the temporal cortex. These results suggest that (i) semantic features of a word are retained as a set of neural oscillations at specific frequencies and (ii) memorizing words sharing a common semantic feature produces harmonic brain responses through a resonance or integration (sharing) of the oscillatory signals.
Perspectives and use of telemedicine by doctors in India: A cross-sectional study
Authors: Nagaraja Vikranth H. , Dastidar Biswanath Ghosh , Suri Shailesh , Jani Anant R.
Published: October 2022

Objectives

India has committed to formulating a roadmap for realising a resilient health system, with digital health being an important element of this. Following the successful implementation of a free telemedicine service, eSanjeevani, India published the Telemedicine Practice Guidelines in 2020 to further scale telemedicine use in India. The main objective of the current study was to understand the perspective and use of telemedicine by medical doctors in India after the release of its telemedicine policy.

Methods

Data were acquired through an anonymous, cross-sectional, internet-based survey of medical doctors (n = 444) at a pan-India level. Replies were subjected to statistical analysis.

Results

Telemedicine was used for various non-mutually exclusive reasons, with the top two reasons being live audio or video consultations (60.4%) and online payments (19.1%) and smartphones were the most frequently used device type (60.6%). The telemedicine benefit that the greatest proportion of respondents (93%) recognised was its potential to reduce COVID-19 infection risk for healthcare professionals. Interestingly, nearly 45% of respondents felt that limited and fragmented insurance coverage was an important limitation to the practice of telemedicine in India and 49% believed reduced patient fees for teleconsultations could help incentivise telemedicine use.

Conclusions

This study helps to appraise the use of telemedicine in India after the publication of telemedicine guidelines in 2020. Furthermore, the findings can inform the development of telemedicine platforms, policies and incentives to improve the design and implementation of effective telemedicine in India.

Public Interest Summary

India has committed to formulating a roadmap for realising a resilient health system, with digital health being an important element of this. In 2020, India published its Telemedicine Practice Guidelines to scale telemedicine use in India. The main objective of the current study was to survey medical doctors in India to understand their perspectives on and use of telemedicine after the release of India’s telemedicine policy. Our findings revealed that the top two reasons doctors used telemedicine were for live audio or video consultations and online payments. Interestingly, a large proportion of respondents felt that limited and fragmented insurance coverage was an important limitation to the practice of telemedicine in India. This study helps to appraise the use of telemedicine in India after the publication of its telemedicine guidelines and can inform the development of telemedicine platforms, policies and incentives to improve the design and implementation of telemedicine in India.
Effectiveness of mRNA-1273 against infection and COVID-19 hospitalization with SARS-CoV-2 Omicron subvariants: BA.1, BA.2, BA.2.12.1, BA.4, and BA.5
Authors: Tseng Hung Fu , Ackerson Bradley K. , Bruxvoort Katia J. , Sy Lina S. , Tubert Julia E. , Lee Gina S. , Ku Jennifer H. , Florea Ana , Luo Yi , Qiu Sijia , Choi Soon Kyu , Takhar Harpreet S. , Aragones Michael , Paila Yamuna D. , Chavers Scott , Talarico Carla A. , Qian Lei
Published: October 2022

Studies have reported reduced natural SARS-CoV-2 infection- and vaccine-induced neutralization against Omicron BA.4/BA.5 compared with earlier Omicron subvariants. We conducted a test-negative case–control study evaluating mRNA-1273 vaccine effectiveness (VE) against infection and hospitalization with Omicron subvariants. The study included 30,809 SARS-CoV-2 positive and 92,427 SARS-CoV-2 negative individuals aged ≥18 years tested during 1/1/2022-6/30/2022. While 3-dose VE against BA.1 infection was high and waned slowly, VE against BA.2, BA.2.12.1, BA.4, and BA.5 infection was initially moderate to high (61.0%-90.6% 14-30 days post third dose) and waned rapidly. The 4-dose VE against infection with BA.2, BA.2.12.1, and BA.4 ranged between 64.3%-75.7%, and was low (30.8%) against BA.5 14-30 days post fourth dose, disappearing beyond 90 days for all subvariants. The 3-dose VE against hospitalization for BA.1, BA.2, and BA.4/BA.5 was 97.5%, 82.0%, and 72.4%, respectively; 4-dose VE against hospitalization for BA.4/BA.5 was 88.5%. Evaluation of the updated bivalent booster is warranted.
Functionally distinct promoter classes initiate transcription via different mechanisms reflected in focused versus dispersed initiation patterns
Authors: Serebreni Leonid , Pleyer Lisa-Marie , Haberle Vanja , Hendy Oliver , Vlasova Anna , Loubiere Vincent , Nemčko Filip , Bergauer Katharina , Roitinger Elisabeth , Mechtler Karl , Stark Alexander
Published: October 2022

Recruitment of RNA polymerase II (Pol II) to promoter regions is essential for transcription. Despite conflicting evidence, the Pol II Pre-Initiation Complex (PIC) is often thought to be of uniform composition and assemble at all promoters via an identical mechanism. Here, we show usingDrosophila melanogasterS2 cells as a model that promoter classes with distinct functions and initiation patterns function via PICs that display different compositions and dependencies: developmental promoter DNA readily associates with the canonical Pol II PIC, whereas housekeeping promoter DNA does not and instead recruit different factors such as DREF. Consistently, TBP and DREF are required by distinct sets of promoters, and TBP and its paralog TRF2 function at different promoter types, partly exclusively and partly redundantly. In contrast, TFIIA is required for transcription from all promoters, and we identify factors that can recruit and/or stabilize TFIIA at housekeeping promoters and activate transcription. We show that promoter activation by these factors is sufficient to induce the dispersed transcription initiation patterns characteristic of housekeeping promoters. Thus, different promoter classes direct distinct mechanisms of transcription initiation, which relate to different focused versus dispersed initiation patterns.
Dual states of Bmi1-expressing intestinal stem cells drive epithelial development and tissue regeneration
Authors: Smith Nicholas R. , Sengupta Sidharth K. , Conley Patrick , Giske Nicole R. , Klocke Christopher , Walker Brett , McPhail Noelle , Swain John R. , Yoo Yeon Jung , Anderson Ashley , Davies Paige S. , Sanati Nasim , Nguyen Theresa N. , Torkenczy Kristof , Adey Andrew C. , Fischer Jared M. , Wu Guanming , Wong Melissa H.
Published: October 2022

Intestinal development, response to injury and disease states rely upon balanced stem cell proliferation. Historically, two subtypes of intestinal epithelial stem cells (ISCs)—slow-cycling/label-retaining, and actively-cycling/canonical Wnt-dependent—coordinate to drive proliferation and regulate epithelial renewal during adult tissue homeostasis and injury response. Recent studies focused on Bmi1-expressing cells revealed that differentiated Bmi1+ enteroendocrine cells could dedifferentiate towards a canonical Wnt-dependent stem cell state, calling into question the dogma that a dual stem cell axis regulates epithelial proliferation. Herein, we identify stem cell function in a Bmi1+ cell population in early murine intestinal development prior to the establishment of canonical Wnt-dependent, Lgr5-expressing ISCs. In-depth analyses of developmental Bmi1+ ISCs using lineage-tracing and single cell RNA-sequencing reveal their distinct identity and capacity to differentiate into Lgr5+ ISCs and other differentiated lineages. Further, during in utero development, the Bmi1+ ISCs initially exists in a highly proliferative state then transitions to a slow-cycling state, with the emergence of actively-cycling Lgr5+ ISCs. In adult tissue, Bmi1+ ISCs are a distinct population that re-express developmental gene and protein profiles, and a non-canonical Wnt signaling signature in response to injury and in human colorectal tumors. Further, developmental Bmi1+ ISCs are distinct from Lgr5+ ISCs and the previously identified differentiated Bmi1+ progenitor cells. Re-evaluation of an under-appreciated Bmi1+ ISC population with fundamental importance in intestinal development re-establishes the importance of the dynamic interplay between discrete ISC populations that are regulated by opposing Wnt signaling pathways. This finding opens opportunities and targetable pathways to augment regeneration or inhibit tumorigenesis.
Maturation of SARS-CoV-2 Spike-specific memory B cells drives resilience to viral escape
Authors: Marzi Roberta , Bassi Jessica , Silacci-Fregni Chiara , Bartha Istvan , Muoio Francesco , Culap Katja , Sprugasci Nicole , Lombardo Gloria , Saliba Christian , Cameroni Elisabetta , Cassotta Antonino , Low Jun Siong , Walls Alexandra C. , McCallum Matthew , Tortorici M. Alejandra , Bowen John E. , Dellota Exequiel A. , Dillen Josh R. , Czudnochowski Nadine , Pertusini Laura , Terrot Tatiana , Lepori Valentino , Tarkowski Maciej , Riva Agostino , Biggiogero Maira , Pellanda Alessandra Franzetti , Garzoni Christian , Ferrari Paolo , Ceschi Alessandro , Giannini Olivier , Havenar-Daughton Colin , Telenti Amalio , Arvin Ann , Virgin Herbert W. , Sallusto Federica , Veesler David , Lanzavecchia Antonio , Corti Davide , Piccoli Luca
Published: October 2022

Memory B cells (MBCs) generate rapid antibody responses upon secondary encounter with a pathogen. Here, we investigated the kinetics, avidity and cross-reactivity of serum antibodies and MBCs in 155 SARS-CoV-2 infected and vaccinated individuals over a 16-month timeframe. SARS-CoV-2-specific MBCs and serum antibodies reached steady-state titers with comparable kinetics in infected and vaccinated individuals. Whereas MBCs of infected individuals targeted both pre- and postfusion Spike (S), most vaccine-elicited MBCs were specific for prefusion S, consistent with the use of prefusion-stabilized S in mRNA vaccines. Furthermore, a large fraction of MBCs recognizing postfusion S cross-reacted with human betacoronaviruses. The avidity of MBC-derived and serum antibodies increased over time resulting in enhanced resilience to viral escape by SARS-CoV-2 variants, including Omicron BA.1 and BA.2 sub-lineages, albeit only partially for BA.4 and BA.5 sublineages. Overall, the maturation of high-affinity and broadly-reactive MBCs provides the basis for effective recall responses to future SARS-CoV-2 variants.
Accelerated signal propagation speed in human neocortical dendrites
Authors: Oláh Gáspár , Lákovics Rajmund , Shapira Sapir , Leibner Yoni , Szűcs Attila , Csajbók Éva Adrienn , Barzó Pál , Molnár Gábor , Segev Idan , Tamás Gábor
Published: October 2022

Human-specific cognitive abilities depend on information processing in the cerebral cortex, where the neurons are significantly larger and their processes longer and sparser compared to rodents. We found that, in synaptically connected layer 2/3 pyramidal cells (L2/3 PCs), the delay in signal propagation from soma to soma is similar in humans and rodents. To compensate for the longer processes of neurons, membrane potential changes in human axons and/or dendrites must propagate faster. Dual somato-dendritic and somato-axonal patch recordings show that the propagation speed of action potentials (APs) is similar in human and rat axons, but the forward propagation of excitatory postsynaptic potentials (EPSPs) and the backward propagation of APs are 26 and 47% faster in human dendrites, respectively. Accurate biophysical models of human and rat L2/3 PCs, combined with pharmacological manipulations of membrane properties, have shown that various factors enhance EPSP propagation in humans; the key factor is the large conductance load imposed by the large basal dendritic tree in humans, the key factor responsible for the accelerated signal propagation in human cortical dendrites. Larger dendritic diameter in humans as well as differences in cable and ion channel properties, also contribute to the enhancement of signal propagation in human L2/3 dendrites.
Novel and simple simulation method to design and development of antisense template
Authors: Deo Devendra Vilas , Shaikh Nawaj
Published: October 2022

Antisense technology is emerging as potential therapeutics against lethal infections. Basically, Antisense-mRNA complex inhibits the protein translation of pathogens and thus it is used for treatment. Based on previous online tools and literatures and difficulties for designing antisense template, finding high conserved regions from large number of long sequences, by taking all those factors in consideration, we proposed new innovative offline target simulation methods i.e. Deletion of unwanted region from viral sequence alignment (DURVA) and Most frequent region (MFR) for designing and developing antisense template from large number of long sequence or genomic data. Based on current pandemic crisis and long genomic sequence of SARS-CoV-2, we chose coronavirus for simulation. Initially, we hypothesized that DURVA-MFR would find stable region from large annotated sequencing data. As per Chan et.al. guidelines for antisense designing and development, we designed couple of algorithms and python scripts to process the data of approximately 30kbp sequence length and 1Gb file size in short turnaround time. The steps involved were as: 1) Simplifying whole genome sequence in single line; 2) Deletion of unwanted region from Virus sequence alignment(DURVA); 3)Most frequent antisense target region(MFR) and 4)Designing and development of antisense template. This simulation method is identifying most frequent regions between 20-30bp long, GC count≥10. Our study concluded that targets were highly identical with large population and similar with high number of remaining sequences. In addition, designed antisense sequences were stable and each sequence is having tighter binding with targets. After studying each parameter, here we suggested that our proposed method would be helpful for finding best antisense against all present and upcoming lethal infection.The initial design of this logic was published in Indian Patent Office Journal No.08/2021withApplication number202121005964A.

Simple summary

The antisense development is state of the art for modern therapeutics. There are number of online soft-wares and open sources for designing of antisense template. But all other tools did not consider frequency as major factor for designing antisense. Also; all sources excepting our simulation approach does not process large file or long sequences. Therefore; we designed an offline innovative simulation method which deletes the unwanted region from sequences and stores the data which are fulfilled antisense criteria. Further; the calculation of frequency from these short listed target regions; the most frequent region is desire antisense target and further antisense template will be designed according to Watson-Crick model. This article explained all information about how our new approach is best for designing antisense template against SARS-CoV-2 and many lethal infectious viruses etc.
Global transmission of Salmonella enterica serovars associated with historical pork trade via Euramerica centralized sourcing
Authors: Wu Yilei , Zhong Lin , Li Shengkai , Li Heng
Published: October 2022

Past decades have witnessed swine as the common sources of Salmonella enterica infections. Nevertheless, how Salmonella enterica entered food supply chains and caused foodborne outbreaks remains to be excluded. By analysis of 718 publicly Salmonella enterica isolates, we demonstrated that Euramerica act as the centralized sourcing for the global spread of Salmonella enterica which origins at the pinnacle of pork production. Specifically, the lineage of Salmonella Choleraesuis lend geographic support for their dispersal from Euramerica centralized origins. We used the generalized linear model to quantify the relative contributions of potential explanatory variables to the global transmission of Salmonella enterica. The global pork trade may act as the key driver for the geographic dispersal of Salmonella enterica over the world. In addition, the application of antimicrobials over the past 80 years may also exert a large impact on the evolution of Salmonella enterica genomics. Taken together, our findings provided the global lineage evolution of Salmonella enterica. Further investigation and potential intervention are needed to identify the global spread of Salmonella enterica over the world.
Use of Transient Transfection for cGMP Manufacturing of eOD-GT8 60mer, a Self-Assembling Nanoparticle Germline-Targeting HIV-1 Vaccine Candidate
Authors: Sharma Vaneet K. , Tsvetnitsky Vadim , Menis Sergey , Brower Evan T. , Sayeed Eddy , Ackland Jim , Lombardo Angela , Hassell Thomas , Schief William R.
Published: October 2022

We describe the current Good Manufacturing Practice (cGMP) production and subsequent characterization of eOD-GT8 60mer, a glycosylated self-assembling nanoparticle HIV-1 vaccine candidate germline-targeting priming immunogen. Production was carried out by transient expression in the human embryonic kidney 293 (HEK293) cell line followed by a combination of purification techniques. A large scale cGMP (200 L) production run yielded 354 mg of the purified eOD-GT8 60mer drug product material, which was formulated at 1 mg/mL in 10% sucrose in phosphate-buffered saline (PBS) at pH 7.2. The clinical trial material was comprehensively characterized for purity, antigenicity, glycan composition, amino acid sequence, aggregation, and by several safety-related tests during cGMP lot release. A comparison of purified products produced at 1 L scale and 200 L cGMP scale demonstrated consistency and robustness of the transient transfection upstream process and the downstream purification strategies. The cGMP clinical trial material is being tested in a phase 1 clinical trial (NCT03547245) and is currently stored at −80°C and on a stability testing program as per regulatory guidelines. The methods described here illustrate the utility of transient transfection for cGMP production of complex products such as glycosylated self-assembling nanoparticles.
DNA methyltransferase inhibition induces dynamic gene expression changes in lung CD4+T cells of neonatal mice withE. colipneumonia
Authors: Michki Nigel S. , Ndeh Roland , Helmin Kathryn A. , Singer Benjamin D. , McGrath-Morrow Sharon A.
Published: October 2022

Introduction

Bacterial pulmonary infections are a major cause of morbidity and mortality in neonates, with less severity in older children. Previous studies demonstrated that the DNA of CD4+T cells in the mouse lung, whose primary responsibility is to coordinate the immune response foreign pathogens, is differentially methylated in neonates compared with juveniles. Nevertheless, the effect of this differential DNA methylation on CD4+T cell gene expression and response to infection remains unclear.

Methods

We treatedE. coli-infected neonatal (4-day-old) and juvenile (13-day-old) mice with decitabine (DAC), a DNA methyltransferase inhibitor with broad-spectrum DNA demethylating activity, and performed simultaneous genome-wide DNA methylation and transcriptional profiling on lung CD4+T cells.

Results

Juvenile and neonatal mice experienced differential demethylation in response to DAC treatment, with larger methylation differences observed in neonates. By cross-filtering differentially expressed genes between juveniles and neonates with those sites that were demethylated in neonates, we found that interferon-responsive genes such asIfit1are the most down-regulated methylation-sensitive genes in neonatal mice. DAC treatment shifted neonatal lung CD4+T cells toward a gene expression program similar to that of juveniles.

Conclusion

Following lung infection withE. coli, lung CD4+T cells in neonatal mice exhibit epigenetic repression of important host defense pathways, which are activated by inhibition of DNA methyltransferase activity to resemble a more mature profile.
Expansion Segment ES30L enriched in birds and mammals can potentially regulate protein synthesis
Authors: Hariharan Nivedita , Ghosh Sumana , Nallan Aditi N. , Ramesh Arati , Agashe Deepa , Palakodeti Dasaradhi
Published: October 2022

Ribosomes, the molecular machines that are central to protein synthesis, have gradually been gaining prominence for their regulatory role in translation. Eukaryotic cytosolic ribosomes are typically larger than bacterial ones, partly due to multi-nucleotide insertions at specific conserved positions in the ribosomal RNAs (rRNAs). Such insertions called expansion segments (ESs) are present primarily on the ribosomal surface, with their role in translation and its regulation remaining under-explored. One such ES in the ribosomal large subunit (LSU) is ES30L, which is present only in mammals and birds among eukaryotes. In this study, we show that ES30L possesses complementarity to many protein-coding transcripts in humans and that the complementarity is enriched around the start codon, hinting at a possible role in translation regulation. Further, our in silico analysis analyses and pull-down assays indicate that ES30L may bind to secondary structures in the 5’ UTR of several transcripts and RNA binding proteins (RBPs) that are essential for translation. Thus, we have identified a potential regulatory role for ES30L in translation.
Hybrid Synthesis of bioplastics polyhydroxybutyrate from carbon dioxide
Authors: Zhang Jie , Liu Dingyu , Liu Yuwan , Chu Huanyu , Cheng Jian , Zhao Haodong , Fu Shaoping , Huihong Liu , Fu YuE , Ma Yanhe , Jiang Huifneg
Published: October 2022

The accelerating environmental crisis has intensified the demand for switching from traditional economy to a renewable one with a reduced carbon footprint. Here we reported a hybrid system, coupling chemical process of CO2hydrogen reduction and biological process for polyhydroxybutyrate (PHB) synthesis, that utilized CO2as a raw material to produce PHB in vitro. The synthetic pathway of PHB was optimized by screening more efficient methanol oxidases, high activity mutants of glycolaldehyde synthase and coordinating enzyme dosages in the pathway, which achieved the carbon yield of 93.6% for producing PHB from methanol. Finally, by combining with the chemical process from CO2to methanol, a scaling-up bio-system was performed to convert CO2into PHB, yielding 5.8 g/L with the productivity of 1.06 g-1L-1h-1. This approach represents a promising carbon-neutral way to produce biodegradable plastics.
A Zur-mediated transcriptional regulation of the zinc export system
Authors: Ducret Verena , Gonzalez Diego , Leoni Sara , Valentini Martina , Perron Karl
Published: October 2022

The control of cellular zinc (Zn) concentrations by dedicated import and export systems is essential for the survival and virulence ofPseudomonas aeruginosa. The transcription of its many Zn transporters is therefore tightly regulated by a known set of transcription factors involved in either the import or the export of Zn. In this work, we show that the Zur protein, a well-known repressor of Zn import, plays a dual role and functions in both import and export processes. In a situation of Zn excess, Zur represses Zn entry, but also activates the transcription ofczcR, a positive regulator of the Zn export system. To achieve this, Zur binds at two sites, located by DNA footprinting in the region downstream theczcRtranscription start site. In agreement with this regulation, a delay in induction of the efflux system is observed in the absence of Zur and Zn resistance is affected. The discovery of this regulation highlights a new role of Zur as global regulator of Zn homeostasis inP. aeruginosadisclosing an important link between Zur and zinc export.
Dynamic compartmentalization of the pro-invasive transcription factor NHR-67 reveals a role for Groucho in regulating a proliferative-invasive cellular switch inC. elegans
Authors: Medwig-Kinney Taylor N. , Kinney Brian A. , Martinez Michael A. Q. , Yee Callista , Sirota Sydney S. , Mullarkey Angelina A. , Somineni Neha , Hippler Justin , Zhang Wan , Shen Kang , Hammell Christopher M. , Pani Ariel M. , Matus David Q.
Published: October 2022

A growing body of evidence suggests that cell division and basement membrane invasion are mutually exclusive cellular behaviors. How cells switch between proliferative and invasive states is not well understood. Here, we investigated this dichotomyin vivoby examining two cell types in the developingCaenorhabditis eleganssomatic gonad that derive from equipotent progenitors, but exhibit distinct cell behaviors: the post-mitotic, invasive anchor cell and the neighboring proliferative, non-invasive ventral uterine (VU) cells. We show that the fates of these cells post-specification are more plastic than previously appreciated and that levels of NHR-67 are important for discriminating between invasive and proliferative behavior. Transcription ofnhr-67is downregulated following post-translational degradation of its direct upstream regulator, HLH-2 (E/Daughterless) in VU cells. In the nuclei of VU cells, residual NHR-67 protein is compartmentalized into discrete punctae that are dynamic over the cell cycle and exhibit liquid-like properties. By screening for proteins that colocalize with NHR-67 punctae, we identified new regulators of uterine cell fate maintenance: homologs of the transcriptional co-repressor Groucho (UNC-37 and LSY-22), as well as the TCF/LEF homolog POP-1. We propose a model in which association of NHR-67 with the Groucho/TCF complex suppresses the default invasive state in non-invasive cells, which complements transcriptional regulation to add robustness to the proliferative-invasive cellular switchin vivo.
From geology to biology: an interdisciplinary course in crystal growth
Authors: Arkhipov Sergey G. , Bekker Tatyana B. , Gaydamaka Anna A. , Likhacheva Anna Y. , Losev Evgeniy A. , Boldyreva Elena V.
Published: October 2022

This contribution shares experience of teaching an interdisciplinary university course in crystal growth with examples ranging from geology to biology. This is an attempt to combine teaching the basics of the classical and non-classical theories of crystallization with impressive examples of crystals growing around us and in the human body, as well as demonstration of the common phenomena in the growth of minerals in nature, crystalline materials in industry and the laboratory, and biomimetic and stimulus-responsive crystals. Lectures are supported by laboratory exercises. Students can also perform an individual research project and present an oral contribution at a mini-conference. Examples of the topics considered in the course are given, and an extensive list of references to papers and web resources is provided, which may be useful to those who want to implement anything from the authors' experience.
Faster and lower-dose X-ray reflectivity measurements enabled by physics-informed modeling and artificial intelligence co-refinement
Authors: Mareček David , Oberreiter Julian , Nelson Andrew , Kowarik Stefan
Published: October 2022

An approach is presented for analysis of real-time X-ray reflectivity (XRR) process data not just as a function of the magnitude of the reciprocal-space vector q, as is commonly done, but as a function of both q and time. The real-space structures extracted from the XRR curves are restricted to be solutions of a physics-informed growth model and use state-of-the-art convolutional neural networks (CNNs) and differential evolution fitting to co-refine multiple time-dependent XRR curves R(q, t) of a thin film growth experiment. Thereby it becomes possible to correctly analyze XRR data with a fidelity corresponding to standard fits of individual XRR curves, even if they are sparsely sampled, with a sevenfold reduction of XRR data points, or if the data are noisy due to a 200-fold reduction in counting times. The approach of using a CNN analysis and of including prior information through a kinetic model is not limited to growth studies but can be easily extended to other kinetic X-ray or neutron reflectivity data to enable faster measurements with less beam damage.
Janus structures of SMoSe and SVSe compositions with low enthalpy and unusual crystal chemistry
Authors: Gavryushkin Pavel , Sagatov Nursultan , Sukhanova Ekaterina , Medrish Inna , Popov Zakhar
Published: October 2022

The recent synthesis of single-layer Janus-type transition metal dichalcogenides (TMDs) raises the question of the existence of other possible 2D structures with an asymmetric out-of-plane structural configuration. In the present work, a theoretical search for new Janus structures having SMoSe and SVSe compositions is performed. A detailed crystal-chemical analysis of the predicted structures is carried out, and it is shown that some of the dynamically stable structures are characterized by crystal-chemical features that are unique among TMDs, including quadruple Mo—Mo bonds and covalent S—S and Se—Se bonds. It is also shown that Mo-bearing TMDs have a tendency to form strong Mo—Mo bonds with chains or isolated dimers of molybdenum atoms, while in the case of vanadium-containing TMDs this feature is not characteristic. Two predicted crystal structures, called 1M-SVSe and 1A′-SMoSe, are especially promising for experimental synthesis and practical applications owing to their dynamical stability and rather low value of enthalpy compared with known structures. The enthalpy of 1M-SVSe is 0.22 eV per formula unit lower than that of 1T-SVSe, while the enthalpy of 1A′-SMoSe is 0.12 eV per formula unit lower than the enthalpy of 1T-SMoSe. The performed topological analysis showed that the predicted structures are unique and do not have analogues in the Inorganic Crystal Structure Database.
Analysis of time-of-flight small-angle neutron scattering data on mesoscopic crystals such as magnetic vortex lattices
Authors: Campillo Emma , Bartkowiak Maciej , Prokhnenko Oleksandr , Smeibidl Peter , Forgan Edward M. , Blackburn Elizabeth
Published: October 2022

Bragg diffracted intensities and q values for crystalline structures with long repeat distances may be obtained by small-angle neutron scattering (SANS) investigations. An account is given of the methods, advantages and disadvantages of obtaining such data by the multichromatic time-of-flight method, compared with the more traditional quasi-monochromatic SANS method. This is illustrated with data obtained from high-magnetic-field measurements on magnetic vortex line lattices in superconductors on the former HFM/EXED instrument at Helmholtz-Zentrum Berlin. The methods have application to other mesoscopic crystalline structures investigated by SANS instruments at pulsed sources.
Interactions between architects and end-users during housing design processes: a systematic literature review
Authors: Mertens Audrey , Hamarat Yaprak , Elsen Catherine
Published: October 2022

Purpose

This research focuses on the interactions between architects and end-users during the design process of housing projects, both experiencing challenges and friction points when meeting.

Design/methodology/approach

The authors conducted a systematic literature review (SLR), based on and adapted from Kitchenham and Charters' work (2007). The thematic analysis of N = 104 identified articles reveals 13 main themes and 30 subthemes specific to architects, end-users and the interactions of architects and end-users, and 3 main groups of other actors intervening in these dynamics. The authors organize the data by actors and the actors' social encounters, themes and subthemes. The authors focus on some aspects, given possible evolution of practices.

Findings

The authors question the role of architects and the ways both parties share respective knowledge. The authors also discuss the various scales of social encounters depicted through literature, from traditional discursive meetings to participatory practices, and raise the lack of convincing tools genuinely used in current housing architecture practices. Finally, the authors point out the need for further field research in order to practically bridge the gap between researchers and practitioners.

Originality/value

The authors present an overview of the most relevant papers, organized in a table and grouped by themes. This represents a major output of this SLR, and gives the concerned readers the opportunity to get a grasp on readers' sub/theme of interest.
Impact of boredom on perceived inequity and discretionary behaviors: a latent growth curve approach
Authors: Chou Shih Yung , Han Bo , Ramser Charles
Published: October 2022

Purpose

This study seeks to examine the effect of work-related boredom and a perceived lack of external stimulation on benevolent and entitled employees' perceived inequity and discretionary workplace behaviors.

Design/methodology/approach

A total of 668 useable three-wave panel data were obtained via Amazon Mechanical Turk during a three-month period. The hypothesized model was tested using a latent growth curve modeling via EQS 6.4 for Windows.

Findings

This study finds the following results. First, benevolent employees who experience higher initial work-related boredom report positive inequity. Second, entitled employees who experience higher initial work-related boredom and a perceived lack of external stimulation report negative inequity. Third, increases in work-related boredom and a perceived lack of external stimulation result in a faster increase in entitled employees' perceived negative inequity. Fourth, entitled employees who perceive higher negative inequity at the initial measurement period report higher interpersonal deviance. Finally, increases in entitled employees' perceived negative inequity result in a faster increase in interpersonal deviance.

Originality/value

This study highlights how employees may assess their effort and rewards when experiencing boredom. This study also offers some practical recommendations that help human resource managers manage boredom in the organization effectively.