Miracle-dz/UniFAR-FTUs huggingface dataset:
Calpain DEK1 acts as a developmental switch gatekeeping cell fate transitions

Calpains are cysteine proteases that control cell fate transitions. Although calpains are viewed as modulatory proteases displaying severe, pleiotropic phenotypes in eukaryotes, human calpain targets are also directed to the N-end rule degradatory pathway. Several of these destabilized targets are transcription factors, hinting at a gene regulatory role. Here, we analyze the gene regulatory networks of Physcomitrium patens and characterize the regulons that are deregulated in DEK1 calpain mutants. Predicted cleavage patterns of regulatory hierarchies in the five DEK1-controlled subnetworks are consistent with the gene’s pleiotropy and the regulatory role in cell fate transitions targeting a broad spectrum of functions. Network structure suggests DEK1-gated sequential transition between cell fates in 2D to 3D development. We anticipate that both our method combining phenotyping, transcriptomics and data science to dissect phenotypic traits and our model explaining the calpain’s role as a switch gatekeeping cell fate transitions will inform biology beyond plant development.
Abstract 3917: A novel multifunctional role for Hsp70 in binding post-translational modifications on client proteins

Hsp70 interactions are critical for cellular viability and the response to stress. Previous attempts to characterize Hsp70 interactions have been limited by their transient nature and inability of current technologies to distinguish direct vs bridged interactions. We report the novel use of cross-linking mass spectrometry (XL-MS) to comprehensively characterize the budding yeast Hsp70 protein interactome. In doing so, we have uncovered not only a new set of Hsp70 client proteins but show that these clients bind at multiple sites on Hsp70, including the N-terminal NBD. Notably, many of the Hsp70 interactions with client proteins are in close proximity to biologically important post translational modifications (PTMs). Using this approach, we have gained fundamental new insights into Hsp70 function, including definitive evidence of Hsp70 self-association as well as multi-point interaction with its client proteins. In addition to identifying a novel set of direct Hsp70 interactors which can be used to probe chaperone function in cells, we have also identified a suite of PTM-associated Hsp70 interactions. The majority of these PTMs have not been previously reported and appear to be critical in the regulation of client protein function. These data indicate that one of the mechanisms by which PTMs contribute to protein function is by facilitating interaction with chaperones. Taken together, we propose that XL-MS analysis of chaperone complexes may be used as a unique way to identify biologically important PTMs on client proteins. All in all, our data suggest that our XL-MS approach to chaperone interactome characterization can also be used as a novel way to identify biologically important and previously unknown PTMs on client proteins. Citation Format: Nitika, Jake Kline, Luca Fornelli, Andrew Truman. A novel multifunctional role for Hsp70 in binding post-translational modifications on client proteins [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3917.
Woodsmoke particulates alter expression of antiviral host response genes in human nasal epithelial cells infected with SARS-CoV-2 in a sex-dependent manner

We have previously shown that exposure to particulate air pollution, both from natural and anthropogenic sources, alters gene expression in the airways and increases susceptibility to respiratory viral infection. Additionally, we have shown that woodsmoke particulates (WSP) affect responses to influenza in a sex-dependent manner. In the present study, we used human nasal epithelial cells (hNECs) from both sexes to investigate how particulate exposure could modulate gene expression in the context of SARS-CoV-2 infection. We used diesel exhaust particulate (DEP) as well as WSP derived from eucalyptus or red oak wood. HNECs were exposed to particulates at a concentration of 22 μg/cm2 for 2 h then immediately infected with SARS-CoV-2 at a MOI (multiplicity of infection) of 0.5. Exposure to particulates had no significant effects on viral load recovered from infected cells. Without particulate exposure, hNECs from both sexes displayed a robust upregulation of antiviral host response genes, though the response was greater in males. However, WSP exposure before infection dampened expression of genes related to the antiviral host response by 72 h post infection. Specifically, red oak WSP downregulated IFIT1, IFITM3, IFNB1, MX1, CCL3, CCL5, CXCL11, CXCL10, and DDX58, among others. After sex stratification of these results, we found that exposure to WSP prior to SARS-CoV-2 infection downregulated anti-viral gene expression in hNECs from females more so than males. These data indicate that WSP, specifically from red oak, alter virus-induced gene expression in a sex-dependent manner and potentially suppress antiviral host defense responses following SARS-CoV-2 infection.
Evolution of host-microbe cell adherence by receptor domain shuffling

Stable adherence to epithelial surfaces is required for colonization by diverse host-associated microbes. Successful attachment of pathogenic microbes via surface adhesin molecules is also the first step in many devastating infections. Despite the primacy of epithelial adherence in establishing host-microbe associations, the evolutionary processes that shape this crucial interface remain enigmatic. Carcinoembryonic antigen associated cell adhesion molecules (CEACAMs) encompass a multifunctional family of vertebrate cell surface proteins which are recurrent targets of bacterial surface adhesins at epithelial surfaces. Here we show that multiple members of the primate CEACAM family exhibit evidence of repeated natural selection at protein surfaces targeted by bacteria, consistent with pathogen-driven evolution. Inter-species diversity of CEACAM proteins, between even closely-related great apes, determines molecular interactions with a range of bacterial adhesins. Phylogenetic analyses reveal that repeated gene conversion of CEACAM extracellular domains during primate divergence plays a key role in limiting bacterial adhesin tropism. Moreover, we demonstrate that gene conversion has continued to shape CEACAM diversity within human populations, with abundant CEACAM1 variants mediating evasion of adhesins from Neisseria gonorrhoeae, the causative agent of gonorrhea. Together this work reveals a mechanism by which gene conversion shapes first contact between microbes and animal hosts.
Prochlorococcus Exudate Stimulates Heterotrophic Bacterial Competition with Rival Phytoplankton for Available Nitrogen

In nutrient-poor habitats, competition for limited resources is thought to select for organisms with an enhanced ability to scavenge nutrients and utilize them efficiently. Such adaptations characterize the cyanobacterium Prochlorococcus, the most abundant photosynthetic organism in the nutrient-limited open ocean. ABSTRACT The marine cyanobacterium Prochlorococcus numerically dominates the phytoplankton community of the nutrient-limited open ocean, establishing itself as the most abundant photosynthetic organism on Earth. This ecological success has been attributed to lower cell quotas for limiting nutrients, superior resource acquisition, and other advantages associated with cell size reduction and genome streamlining. In this study, we tested the prediction that Prochlorococcus outcompetes its rivals for scarce nutrients and that this advantage leads to its numerical success in nutrient-limited waters. Strains of Prochlorococcus and its sister genus Synechococcus grew well in both mono- and cocultures when nutrients were replete. However, in nitrogen-limited medium, Prochlorococcus outgrew Synechococcus but only when heterotrophic bacteria were also present. In the nitrogen-limited medium, the heterotroph Alteromonas macleodii outcompeted Synechococcus for nitrogen but only if stimulated by the exudate released by Prochlorococcus or if a proxy organic carbon source was provided. Genetic analysis of Alteromonas suggested that it outcompetes Synechococcus for nitrate and/or nitrite, during which cocultured Prochlorococcus grows on ammonia or other available nitrogen species. We propose that Prochlorococcus can stimulate antagonism between heterotrophic bacteria and potential phytoplankton competitors through a metabolic cross-feeding interaction, and this stimulation could contribute to the numerical success of Prochlorococcus in nutrient-limited regions of the ocean. IMPORTANCE In nutrient-poor habitats, competition for limited resources is thought to select for organisms with an enhanced ability to scavenge nutrients and utilize them efficiently. Such adaptations characterize the cyanobacterium Prochlorococcus, the most abundant photosynthetic organism in the nutrient-limited open ocean. In this study, the competitive superiority of Prochlorococcus over a rival cyanobacterium, Synechococcus, was captured in laboratory culture. Critically, this outcome was achieved only when key aspects of the open ocean were simulated: a limited supply of nitrogen and the presence of heterotrophic bacteria. The results indicate that Prochlorococcus promotes its numerical dominance over Synechococcus by energizing the heterotroph’s ability to outcompete Synechococcus for available nitrogen. This study demonstrates how interactions between trophic groups can influence interactions within trophic groups and how these interactions likely contribute to the success of the most abundant photosynthetic microorganism.
CST does not evict elongating telomerase but prevents initiation by ssDNA binding

The CST complex (CTC1-STN1-TEN1) has been shown to inhibit telomerase extension of the G-strand of telomeres and facilitate the switch to C-strand synthesis by DNA polymerase alpha-primase (pol α-primase). Recently the structure of human CST was solved by cryo-EM, allowing the design of mutant proteins defective in telomeric ssDNA binding and prompting the reexamination of CST inhibition of telomerase. The previous proposal that human CST inhibits telomerase by sequestration of the DNA primer was tested with a series of DNA-binding mutants of CST and modeled by a competitive binding simulation. The DNA-binding mutants had substantially reduced ability to inhibit telomerase, as predicted from their reduced affinity for telomeric DNA. These results provide strong support for the previous primer sequestration model. We then tested whether addition of CST to an ongoing processive telomerase reaction would terminate DNA extension. Pulse-chase telomerase reactions with addition of either wild-type CST or DNA-binding mutants showed that CST has no detectable ability to terminate ongoing telomerase extension in vitro. The same lack of inhibition was observed with or without pol α-primase bound to CST. These results suggest how the switch from telomerase extension to C-strand synthesis may occur.
Effect of intake acidic and alkaline foods to rats before meeting on the probability of offspring gender

This study was designed to investigate the effects of consumption acidic and alkaline food to determine offspring gender. In total, 20 female albino rats and 5 males were chosen and randomly divided into 5 groups all groups of rats were fed on the experimental diet. After 20 days of special diet, the female rats were mated with males and were separated after pregnancy. The newborn rats’ sexes were determined after delivery. In potatoes group (58%) males and (42%) female rats were born (sex ratio = 1.38) while these rates were (61%) male and (39%) female (sex ratio = 1.56) in potatoes plus K2HPO4 group , in milk group (57%)male and (43%) females (Sex ratio = 1.33), in milk plus CaCO3 (46%)male and (54%) female (Sex ratio = .85) while in control group (47%) male and (53%) female rats were born (sex ratio = .89). (ALT), and (AST) were determined, Serum creatinine, serum uric acid and serum bilirubin measured. Blood analysis included WBC count, and platelet count (PLC). The present results observed that acidic and alkaline food in the diet of rats can have significant effect on the sex ratio of delivered rats’ offspring.
Review on analog/radio frequency performance of advanced silicon MOSFETs

Aggressive gate-length downscaling of the metal-oxide-semiconductor field-effect transistor (MOSFET) has been the main stimulus for the growth of the integrated circuit industry. This downscaling, which has proved beneficial to digital circuits, is primarily the result of the need for improved circuit performance and cost reduction and has resulted in tremendous reduction of the carrier transit time across the channel, thereby resulting in very high cut-off frequencies. It is only in recent decades that complementary metal-oxide-semiconductor (CMOS) field-effect transistor (FET) has been considered as the radio frequency (RF) technology of choice. In this review, the status of the digital, analog and RF figures of merit (FoM) of silicon-based FETs is presented. State-of-the-art devices with very good performance showing low values of drain-induced barrier lowering, sub-threshold swing, high values of gate transconductance, Early voltage, cut-off frequencies, and low minimum noise figure, and good low-frequency noise characteristic values are reported. The dependence of these FoM on the device gate length is also shown, helping the readers to understand the trends and challenges faced by shorter CMOS nodes. Device performance boosters including silicon-on-insulator substrates, multiple-gate architectures, strain engineering, ultra-thin body and buried-oxide and also III-V and 2D materials are discussed, highlighting the transistor characteristics that are influenced by these boosters. A brief comparison of the two main contenders in continuing Moore’s law, ultra-thin body buried-oxide and fin field-effect transistors are also presented. The authors would like to mention that despite extensive research carried out in the semiconductor industry, silicon-based MOSFET will continue to be the driving force in the foreseeable future.
IDENTIFICATION AND MITIGATION OF CHALLENGES TO IMPLEMENT LAST PLANNER SYSTEM IN INDIAN CONSTRUCTION PROJECTS

In recent years projects have increasingly used Last Planner System (LPS) in building construction. However project managers still struggle with figuring out how the LPS could be applied on their specific projects. One main reason for this struggle is that explicit instructions for systematically applying LPS are not available. This seminar aims to identify LPS implementation challenges and an indication of how LPS can be applied. This seminar qualitatively aggregates the results of literature study and 8 case examples from India to identify LPS implementation challenges, Critical success factors and qualitative analysis (RII) of those challenges through questionnaire surrey ( from professionals who has some experience of working with LPS). After identification and analysis of challenges and success factor it is observed that challenges can be mitigated indirectly through minimizing of construction waste. A live case example is taken and causes of wastes is identified for mitigation of challenges that might occur during the implementation of LPS. Besides that some implementation techniques of LPS are proposed for 3 weeks. Main finding of this research are, a) majority of challenges of implementation are due to stubborn attitude, management problem, unskilled labors, non-involvement of stakeholders’ etc. b) challenges can be mitigated directly through improving involvement, pushing workers to adopt news system by training, proper management etc. and indirectly by minimizing waste. 3) The major reasons behind wastes are arrives from management related issues and worker related issues. Index Terms Lean principle, Lean construction, Last Planner System, Challenges of Implementation of LPS, Mitigation, Success factors, Causes of Waste
The Leukocyte Integrin αDβ2 Binds VCAM-1: Evidence for a Binding Interface Between I Domain and VCAM-1

The trafficking of leukocytes through tissues is supported by an interaction between the β2 (CD18) integrins CD11a/CD18 (LFA-1) and CD11b/CD18 (Mac-1) and their ligand ICAM-1. The most recently identified and fourth member of the β2 integrins, αDβ2, selectively binds ICAM-3 and does not appear to bind ICAM-1. We have reported recently that αDβ2 can support eosinophil adhesion to VCAM-1. Here we demonstrate that expression of αDβ2 in a lymphoid cell that does not express α4 integrins confers efficient binding to VCAM-1. In addition, a soluble form of αDβ2 binds VCAM-1 with greater efficiency relative to ICAM-3. The I domain of αD contains a binding site for VCAM-1 since recombinant αD I domain binds specifically to VCAM-1. In addition, αD mAb that block cellular binding to VCAM-1 bind the αD I domain. Using VCAM-1 mutants we have determined that the binding site on VCAM-1 for αDβ2 overlaps with that of α4 integrins. Substitution of VCAM-1 aspartate at position 40, D40, within the conserved integrin binding site, diminishes binding to αDβ2 and abrogates binding to the αD I domain. The corresponding integrin binding site residue in ICAM-3 is also essential to αDβ2 binding. Finally, we demonstrate that αDβ2 can support lymphoid cell adhesion to VCAM-1 under flow conditions at levels equivalent to those mediated by α4β1. These results indicate that VCAM-1 can bind to an I domain and that the binding of αDβ2 to VCAM-1 may contribute to the trafficking of a subpopulation of leukocytes that express αDβ2.
Naturalistische Untersuchung in der (teil-)stationären psychosomatischen Psychotherapie

Hintergrund: Trotz wachsender empirischer Evidenz zur Wirksamkeit in der Behandlung psychischer Erkrankungen sind internetbasierte Interventionen (IBI) mit geringen Akzeptanzund hohen Abbruchraten konfrontiert. Akzeptanzfördernde Interventionen (AFI) stellen eine vielversprechende Maßnahme dar, um die Akzeptanz zukünftiger Nutzer*innen zu verbessern. Die Wirksamkeit von AFI auf die Adhärenz, die maßgeblichen Einfluss auf die Wirksamkeit von IBI hat, wurde bisher in nur wenigen empirischen Untersuchungen überprüft. Ziel der Arbeit (Fragestellung): Ziel der vorliegenden Untersuchung ist die Überprüfung des Einflusses einer AFI auf die Akzeptanz, die initiale Nutzung und die Adhärenz des transdiagnostischen psychodynamischen Online-Selbsthilfeprogramms „Die Kraft der eigenen Emotionen nutzen (KEN-Online)“. Material undMethoden: Es wurden Routinedaten von 231 Patient*innen ausgewertet, die während ihrer (teil-)stationären Behandlung im Rahmen einer ins Routinesetting integrierten AFI das Angebot bekommen haben, KEN-Online behandlungsbegleitend zu nutzen. Im Kohortendesign werden Patient*innen, die an einer AFI teilgenommen haben, mit einer historischen Kontrollgruppe von Patient*innen verglichen, die dieses Angebot nicht erhielten. Zudem wird der Zusammenhang zwischen der Einstellung und der Akzeptanz des Programms in der Untersuchungsgruppe (mit AFI) überprüft. Ergebnisse: Sowohl die Akzeptanz als auch die initiale Nutzung von KEN-Online waren um knapp 20% höher (jeweils p< 0,01) unter den Teilnehmenden der AFI-Gruppe, verglichen mit der Kontrollgruppe. In Bezug auf die Adhärenz von KEN-Online zeigte sich ein kleiner Unterschied dahingehend, dass Teilnehmende der Kontrollgruppe signifikant (p< 0,05) mehr Einheiten abgeschlossen haben als Teilnehmende der Interventionsgruppe. Allerdings war der Anteil der „completer“ von KEN-Online mit 13,4% insgesamt sehr gering. Ein Einfluss der Einstellung auf die Akzeptanz wurde nicht nachgewiesen. Diskussion: Die vorliegende Untersuchung zeigt, dass AFI dazu beitragen können, die Akzeptanz und initiale Nutzung von IBI zu fördern, indem Patient*innen der (teil-)stationären Routineversorgung standardisiert und strukturiert über die Intervention informiert werden. Hinsichtlich der Förderung der Adhärenz sind jedoch zusätzliche Maßnahmen erforderlich.
MULTI-OBJECTIVE OPTIMAL DESIGN OF THE MFW-IPM MACHINE FOR IMPROVE FLUX-WEAKENING ABILITY

In this paper, a novel mechanical-flux-weakening interior permanent magnet (MFW-IPM) machine is proposed to improve flux-weakening ability. The key of the proposed machine is that the permanent magnet is rotatable, and a mechanical device is equipped on both sides of the rotor. The mechanical device can regulate the air-gap magnetic field by rotating PM to change the leakage flux and magnetization direction of PM. As a result, the flux-weakening ability is improved. The flux-weakening principle of the MFW-IPM machine is investigated in detail. In addition, a multi-objective optimization method is adopted to improve the performance of the proposed machine. Then, the electromagnetic performances of the original machine and optimized machine are compared by finite element analysis. Finally, both simulation results and experimental tests verify the effectiveness of the flux-weakening enhancement design and optimization method.
Calculations of mixing enthalpy and mismatch entropy for ternary amorphous alloys : Special issue on bulk amorphous, nano-crystalline and nano-quasicrystalline alloys

Chemical mixing enthalpy (ΔH chem ) and mismatch entropy normalized by Boltzmann constant (S σ /k B ) corresponding to the three empirical rules for the achievement of high amorphous-forming ability (AFA) were calculated with thermodynamical functions for the gross number of 6450 alloys in 351 ternary amorphous systems. The temary amorphous alloys have ΔH chem of -86 to 25 kJ/mol and S σ /k B of 1.0 × 10 -3 to 5.7. The average values of ΔH chem and S σ /k B are calculated to be -33 kJ/mol and 0.33, respectively. The 30 alloys in 9 ternary amorphous systems including 10 alloys in Ag-Cu-Fe system have positive values of ΔH chem . Most of the ternary amorphous alloys have the values of ΔH chem and S σ /k B inside a trapezoid regicn in ΔH chem - log(S σ /k B ) chart except mainly for the H- and the C-containing alloys. Si-W-Zr system and the 32 alloys having positive values of ΔH chem . The analysis of AFA was carried out for typical five ternary amorphous systems. The following four results are derived. 1) Al-La-Ni and B-Fe-Zr alloys have high AFA in accordance with the concept of the three empirical rules. 2) The further multiplication of alloy components causes an increase in the AFA of Al-B-Fe alloys. 3) Thermodynamical factors represented by melting temperature and viscosity at the melting temperature are required for evaluation of AFA for Mg- and Pd-based amorphous alloys. 4) A tendency for log(S σ /k B ) to increase with decreasing ΔH chem is recognized in each alloys system, implying the stabilization of an amorphous phase against solid solution and intermediate phase.