bluuebunny/crossref_metadata_2025_split huggingface dataset:
Overview of The Current Progress of Facultative Anaerobic Bacteria in Cancer Biotherapy with TNF-α as Main Mechanism of Action
Authors: Johansson Martina , Nystrom Fredrik H 
Published: April 2021

AbstractThis review article focuses on the use of infectious bacteria as delivery tool for tumour necrosis factor α (TNF-α), a well-studied cytokine, in the context of immunotherapy for cancer treatment. The tumour targeting properties of certain bacteria strains has been known for decades as well as the tumour catabolizing effect of TNF-α. The combination of these two have been studied in murine models for various types of cancer with promising results. Research in this fascinating field is unfortunately uncommon, thus the number of high-quality articles is limited. Search was done via Google Scholar in combination with PubMed, to increase the coverage and find peer-reviewed, original, and primary research articles.Key findings show that attenuated or genetically modified species of bacteria have fewer side effects and can be effective in delivering cytokines to tumour sites. TNF-α is produced by macrophages/monocytes during acute inflammation or infection, thus can be triggered by infectious bacteria which in turn induce apoptosis. The cytotoxic effect of the bacteria can be enhanced with localized irradiation. Promising results have been shown in bladder, breast, colon, glial, lung, ovarian, pancreatic, prostate, and renal cancer cells.The need for better, safer, and more effective cancer treatment is apparent as traditional chemotherapy and radiation can cause a lot of harm for the patient, and not necessarily prolong the lifespan. The success-rate for these treatments vary greatly depending on the type of cancer, but for tumours that cannot be surgically removed the outcome is generally quite poor. A drawback of chemotherapy is that tumours can grow resistant to the treatment while healthy cells continue to be exposed, increasing the risk of severe side effects. Different types of biological therapies are a modern and possibly safer approach, even though immunotherapy comes with substantial risks. Using the innate immune system to fight tumour cells is not always safe, because uncontrolled and excessive release of pro-inflammatory signalling molecules can result in multisystem organ failure and death. This phenomenon is called cytokine release syndrome (cytokine storm) and is one of the major risks of immunotherapy. However, tailored biological therapies have proven their effectiveness for a wide range of cancer types, and the next step in this evolution is to genetically engineer both delivery systems and mechanisms of action. This approach can be combined with the traditional radiation and chemotherapy for increased effectiveness, even if biological therapies as a stand-alone treatment, can be a goal for the future.
Design considerations for workflow management systems use in production genomics research and the clinic
Authors: Ahmed Azza E , Allen Joshua M , Bhat Tajesvi , Burra Prakruthi , Fliege Christina E , Hart Steven N , Heldenbrand Jacob R , Hudson Matthew E , Istanto Dave Deandre , Kalmbach Michael T , Kapraun Gregory D , Kendig Katherine I , Kendzior Matthew Charles , Klee Eric W , Mattson Nate , Ross Christian A , Sharif Sami M , Venkatakrishnan Ramshankar , Fadlelmola Faisal M , Mainzer Liudmila S 
Published: April 2021

ABSTRACTBackgroundThe changing landscape of genomics research and clinical practice has created a need for computational pipelines capable of efficiently orchestrating complex analysis stages while handling large volumes of data across heterogeneous computational environments. Workflow Management Systems (WfMSs) are the software components employed to fill this gap.ResultsThis work provides an approach and systematic evaluation of key features of popular bioinformatics WfMSs in use today: Nextflow, CWL, and WDL and some of their executors, along with Swift/T, a workflow manager commonly used in high-scale physics applications. We employed two use cases: a variant-calling genomic pipeline and a scalability-testing framework, where both were run locally, on an HPC cluster, and in the cloud. This allowed for evaluation of those four WfMSs in terms of language expressiveness, modularity, scalability, robustness, reproducibility, interoperability, ease of development, along with adoption and usage in research labs and healthcare settings. This article is trying to answer,“which WfMS should be chosen for a given bioinformatics application regardless of analysis type?”.ConclusionsThe choice of a given WfMS is a function of both its intrinsic language and engine features. Within bioinformatics, where analysts are a mix of dry and wet lab scientists, the choice is also governed by collaborations and adoption within large consortia and technical support provided by the WfMS team/community. As the community and its needs continue to evolve along with computational infrastructure, WfMSs will also evolve, especially those with permissive licenses that allow commercial use. In much the same way as the dataflow paradigm and containerization are now well understood to be very useful in bioinformatics applications, we will continue to see innovations of tools and utilities for other purposes, like big data technologies, interoperability, and provenance.
Stimulation with mycobacterial glycolipids and PPD reveals different innate immune response profiles in active and latent TB
Authors: Silva Carolina S , Sundling Christopher , Folkeson Elin , Fröberg Gabrielle , Nobrega Claudia , Canto-Gomes João , Chambers Benedict J. , Lakshmikanth Tadepally , Brodin Petter , Bruchfeld Judith , Nigou Jerome , Correia-Neves Margarida , Källenius Gunilla 
Published: April 2021

AbstractUpon infection withMycobacterium tuberculosis(Mtb) the host immune response might clear the bacteria, control its growth leading to latent tuberculosis (LTB), or fail to control its growth resulting in active TB (ATB). There is however no clear understanding of the features underlying a more or less effective response. Mtb glycolipids are abundant in the bacterial cell envelope and modulate the immune response to Mtb, but the patterns of response to glycolipids are still underexplored. To identify the CD45+leukocyte activation landscape induced by Mtb glycolipids in peripheral blood of ATB and LTB, we performed a detailed assessment of the immune response of PBMCs to the Mtb glycolipids lipoarabinomannan (LAM) and its biosynthetic precursor phosphatidyl-inositol mannoside (PIM), and PPD. At 24 h and 5 days of stimulation, cell profiling and secretome analysis was done using mass cytometry and high-multiplex immunoassay. PIM mainly affected antigen-presenting cells to produce both proinflammatory (IL-2, IL-6, IL-17A, TNF-αand GM-CSF), and IL-4 and IL-10 cytokines, but not IFN-γ. LAM triggered a similar, albeit weaker, response. By contrast, PPD induced an increase in IFN-γ-producing cells. Moreover, PPD also led to increased numbers of IL-2, IL-6, IL-10, IL-17A, TNF-αand GrzB-producing cells. Treatment with an anti-TLR2 antibody led to partial inhibition of PIM-induced IL-6 production in myeloid cells, suggesting that PIM induces IL-6 production through TLR2. Expansion of monocyte subsets in response to PIM or LAM was reduced in both ATB and LTB as compared to healthy controls, suggesting a hyporesponsive/tolerance pattern in Mtb-infected individuals.
Collective border cell migration requires the zinc transporter Catsup to limit endoplasmic reticulum stress
Authors: Guo Xiaoran , Dai Wei , Montell Denise 
Published: April 2021

AbstractCollective cell migration is critical for normal development, wound healing, and in tumor progression and metastasis. Border cells in the Drosophila ovary provide a genetically tractable model to identify molecular mechanisms that drive this important cell behavior. In an unbiased screen for defects in border cell migration in mosaic clones, we identified a mutation in thecatsupgene. Catsup, the Drosophila ortholog of Zip7, is a large, multifunctional, transmembrane protein of the endoplasmic reticulum (ER), which has been reported to negatively regulate catecholamine biosynthesis, to regulate Notch signaling, to function as a zinc transporter, and to limit ER stress. Here we report thatcatsupknockdown caused ER stress in border cells and that ectopic induction of ER stress was sufficient to block migration. Notch and EGFR trafficking were also disrupted. Wild type Catsup rescued the migration defect but point mutations known to disrupt the zinc ion transport of Zip7 did not. We conclude that migrating cells are particularly susceptible to defects in zinc transport and ER homeostasis.
Single-Molecule Tracking of Chromatin-Associated Proteins in the C. elegans Gonad
Authors: von Diezmann Lexy , Rog Ofer 
Published: April 2021

1.AbstractBiomolecules are distributed within cells by molecular-scale diffusion and binding events that are invisible in standard fluorescence microscopy. These molecular search kinetics are key to understanding nuclear signaling and chromosome organization, and can be directly observed by single-molecule tracking microscopy. Here, we report a method to track individual proteins within intact C. elegans gonads and apply it to study the molecular dynamics of the axis, a proteinaceous backbone that organizes meiotic chromosomes. Using either fluorescent proteins or enzymatically ligated dyes, we obtain multi-second trajectories with a localization precision of 15-25 nm in nuclei actively undergoing meiosis. Correlation with a reference channel allows for accurate measurement of protein dynamics, compensating for movements of the nuclei and chromatin within the gonad. We find that axis proteins exhibit either static binding to chromatin or free diffusion in the nucleoplasm, and we separately quantify the motion parameters of these distinct populations. Freely diffusing axis proteins selectively explore chromatin-rich regions, suggesting they are circumventing the central phase-separated region of the nucleus. This work demonstrates that single-molecule microscopy can infer nanoscale-resolution dynamics within living tissue, expanding the possible applications of this technique.
Dynamic prospect theory - two core economic decision theories coexist in the gambling behavior of monkeys
Authors: Tymula Agnieszka , Imaizumi Yuri , Kawai Takashi , Kunimatsu Jun , Matsumoto Masayuki , Yamada Hiroshi 
Published: April 2021

AbstractResearch in behavioral economics and reinforcement learning has given rise to two influential theories describing human economic choice under uncertainty. The first, prospect theory, assumes that decision-makers usestaticmathematical functions, utility and probability weighting, to calculate the values of alternatives. The second, reinforcement learning theory, posits thatdynamicmathematical functions update the values of alternatives based on experience through reward prediction error (RPE). To date, these theories have been examined in isolation without reference to one another. Therefore, it remains unclear whether RPE affects a decision-maker’s utility and/or probability weighting functions, or whether these functions are indeed static as in prospect theory. Here, we propose a dynamic prospect theory model that combines prospect theory and RPE, and test this combined model using choice data on gambling behavior of captive macaques. We found that under standard prospect theory, monkeys, like humans, had a concave utility function. Unlike humans, monkeys exhibited a concave, rather than inverse-S shaped, probability weighting function. Our dynamic prospect theory model revealed that probability distortions, not the utility of rewards, solely and systematically varied with RPE: after a positive RPE, the estimated probability weighting functions became more concave, suggesting more optimistic belief about receiving rewards and over-weighted subjective probabilities at all probability levels. Thus, the probability perceptions in laboratory monkeys are not static even after extensive training, and are governed by a dynamic function well captured by the algorithmic feature of reinforcement learning. This novel evidence supports combining these two major theories to capture choice behavior under uncertainty.Significance statementWe propose and test a new decision theory under uncertainty by combining pre-existing two influential theories in the neuroeconomics: prospect theory from economics and prediction error theory from reinforcement learning. Collecting a large dataset (over 60,000 gambling decisions) from laboratory monkeys enables us to test the hybrid model of these two core decision theories reliably. Our results showed over-weighted subjective probabilities at all probability levels after lucky win, indicating that positive prediction error systematically bias decision-makers more optimistically about receiving rewards. This trial-by-trial prediction-error dynamics in probability perception provides outperformed performance of the model compared to the standard static prospect theory. Thus, both static and dynamic elements coexist in monkey’s risky decision-making, an evidence contradicting the assumption of prospect theory.
Relish plays a dynamic role in the niche to modulateDrosophilablood progenitor homeostasis in development and infection
Authors: Ramesh Parvathy , Dey Nidhi Sharma , Kanwal Aditya , Mandal Sudip , Mandal Lolitika 
Published: April 2021

AbstractImmune challenges demand the gearing up of basal hematopoiesis to combat infection. Little is known about how during development, this switch is achieved to take care of the insult. Here, we show that the hematopoietic niche of the larval lymph gland ofDrosophilasenses immune challenge and reacts to it quickly through the nuclear factor-κB (NF-κB), Relish, a component of the immune deficiency (Imd) pathway. During development, Relish is triggered by ecdysone signaling in the hematopoietic niche to maintain the blood progenitors. Loss of Relish causes an alteration in the cytoskeletal architecture of the niche cells in a Jun Kinase dependent manner, resulting in the trapping of Hh implicated in progenitor maintenance. Notably, during infection, downregulation of Relish in the niche tilts the maintenance program towards precocious differentiation, thereby bolstering the cellular arm of the immune response.
Single-molecule imaging of cytoplasmic dyneinin celluloreveals the mechanism of motor activation and cargo movement
Authors: Tirumala Nireekshit Addanki , Redpath Gregory , Skerhut Sarah Viktoria , Dolai Pritha , Kapoor-Kaushik Natasha , Ariotti Nicholas , Kumar K Vijay , Ananthanarayanan Vaishnavi 
Published: April 2021

AbstractCytoplasmic dynein 1 (dynein) is the primary minus end-directed motor protein in most eukaryotic cells. Dynein remains in an inactive conformation until the formation of a tripartite complex comprising dynein, its regulator dynactin and a cargo adaptor. How this process of dynein activation occurs is unclear, since it entails the formation of a three-protein complex inside the crowded environs of a cell. Here, we employed live-cell, single-molecule imaging to visualise and track fluorescently tagged dynein. First, we observed that only ~30% of dynein molecules that bound to the microtubule (MT) engaged in minus end-directed movement, and that too for a short duration of ~0.6 s. Next, using high-resolution imaging in live and fixed cells, and using correlative light and electron microscopy, we discovered that dynactin and endosomal cargo remained in proximity to each other and to MTs. We then employed two-colour imaging to visualise cargo movement effected by single motor binding. Finally, we performed long-term imaging to show short movements are sufficient to drive cargo to the perinuclear region of the cell. We then used these discoveries as the basis for a stochastic model incorporating dynamic motors binding to cargo located along MTs, and also developed a coarse-grained 3-state run- and-tumble particle (RTP) model for the cargo that quantitatively recapitulates the emergent statistics of cargo movement. Taken together, we discovered a search mechanism that is facilitated by dynein’s frequent MT binding-unbinding kinetics: (1) in a futile event when dynein does not encounter cargo anchored in proximity to the MT, dynein dissociates and diffuses into the cytoplasm, (2) when dynein encounters cargo and dynactin upon MT-binding, it moves cargo in a short run. Several of these short runs are undertaken in succession for long-range directed movement. In conclusion, we demonstrate that dynein activation and cargo capture are coupled in a step that relies on the reduction of dimensionality to enable minus end-directed transportin cellulo, and that complex cargo behaviour emerges from stochastic motor-cargo interactions.
Identification of arginine phosphorylation inMycolicibacterium smegmatis
Authors: Ogbonna Emmanuel C. , Anderson Henry R. , Schmitz Karl R. 
Published: April 2021

AbstractTuberculosis is a leading cause of worldwide infectious mortality. The prevalence of multidrug-resistantMycobacterium tuberculosis(Mtb) infections drives an urgent need to exploit new drug targets. One such target is the ATP-dependent protease ClpC1P1P2, which is strictly essential for viability. However, few proteolytic substrates of mycobacterial ClpC1P1P2 have been identified to date. Recent studies inBacillus subtilishave shown that the orthologous ClpCP protease recognizes proteolytic substrates bearing post-translational arginine phosphorylation. While several lines of evidence suggest that ClpC1P1P2 is similarly capable of recognizing phosphoarginine-bearing proteins, the existence of phosphoarginine modifications in mycobacteria has remained in question. Here, we confirm the presence of post-translational phosphoarginine modifications inMycolicibacterium smegmatis(Msm), a nonpathogenic surrogate ofMtb. Using a phosphopeptide enrichment workflow coupled with shotgun phosphoproteomics, we identify arginine phosphosites on several functionally diverse targets within theMsmproteome. Interestingly, phosphoarginine modifications are not upregulated by heat stress, suggesting divergent roles in mycobacteria andBacillus. Our findings provide new evidence supporting the existence of phosphoarginine-mediated proteolysis by ClpC1P1P2 in mycobacteria and other actinobacterial species.
Magnetic wire active microrheology of human respiratory mucus
Authors: Radiom Milad , Hénault Romain , Mani Salma , Iankovski Aline Grein , Norel Xavier , Berret Jean-François 
Published: April 2021

AbstractMucus is a viscoelastic gel secreted by the pulmonary epithelium in the tracheobronchial region of the lungs. The coordinated beating of cilia in contact with the gel layer moves mucus upwards towards pharynx, removing inhaled pathogens and particles from the airways. The efficacy of this clearance mechanism depends primarily on the rheological properties of mucus. Here we use a magnetic wire based microrheology technique to study the viscoelastic properties of human mucus collected from human bronchus tubes. The response of wires between 5 and 80 µm in length to a magnetic rotating field is monitored by optical time-lapse microscopy and analyzed using constitutive equation models of rheology, including Maxwell and Kelvin-Voigt. The static shear viscosity and elastic modulus can be inferred from low frequency (10−3− 10 rad s−1) measurements, leading to the evaluation of the mucin network relaxation time. This relaxation time is found to be widely distributed, from one to several hundred seconds. Mucus is identified as a viscoelastic liquid with an elastic modulus of 2.5 ± 0.5 Pa and a static viscosity of 100 ± 40 Pa s. Our work shows that beyond the established spatial variations in rheological properties due to microcavities, mucus exhibits secondary inhomogeneities associated with the relaxation time of the mucin network that may be important for its flow properties.
The accuracy of NMR protein structures in the Protein Data Bank
Authors: Fowler Nicholas J , Sljoka Adnan , Williamson Mike P 
Published: April 2021

AbstractWe recently described a method, ANSURR, for measuring the accuracy of NMR protein structures. It is based on comparing residue-specific measures of rigidity from backbone chemical shifts via the random coil index, and from structures. Here, we report the use of ANSURR to analyse NMR ensembles within the Protein Data Bank (PDB). NMR structures cover a wide range of accuracy, which improved over time until about 2005, since when accuracy has not improved. Most structures have accurate secondary structure, but are too floppy, particularly in loops. There is a need for more experimental restraints in loops. The best current accuracy measures are Ramachandran distribution and number of NOE restraints per residue. The precision of structure ensembles correlates with accuracy, as does the number of hydrogen bond restraints per residue. If a structure contains additional components (such as additional polypeptide chains or ligands), then their inclusion improves accuracy. Analysis of over 7000 PDB NMR ensembles is available via our websiteansurr.com.
Millennial turnover intentions: how can B-schools make a difference?
Authors: Acharya Pragnya , Garcia-Tapial Joaquin , Jena Lalatendu Kesari 
Published: April 2021

Purpose
The article intends to instigate a new thought process for management institutions to reshape their curriculum and design their teaching around mitigating the rising attrition among millennials. As there is a huge influx of millennials into the corporate world, it is much required that we concentrate on the quality of talent produced and ensure that this talent gives long term results for organizations aiming at a sustained development for both, the organizations as well as the millennial workforce.

Design/methodology/approach
A survey was carried out to seek views from academicians and senior practitioners, who often work as mediating and moderating factors in the process.

Findings
The managers need to understand that apart from developing retention strategies, the target employees should also have the intention to stay, which cannot be instilled by the organization and should be taught along with their management education. It is only to save the time and money of the organization and easing their struggles by developing at the grass-root level, which is in the classrooms where the managers are created.

Originality/value
Much research has been done on revamping teaching pedagogy and including more industry-specific skills into the management education. This article seeks to pin point the attitudinal development of the outgoing managers, which has a high intention towards job hopping.