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  [...]even in the AcMNPV genome, roughly half of the genes have no assigned function, meaning that there are probably many more interesting baculovirus accessory genes whose functions are waiting to be discovered. Since BV can bind to and enter many kinds of vertebrate and invertebrate cells, baculovirus host range is more complex than just receptor binding, and the determinants of host range are poorly characterized. [...]invertebrate antiviral immunity is still a young field, and little is known about immune responses of insects against baculoviruses.

This meta-analysis sought to expand upon neurobiological models of mindfulness through investigation of inherent brain network connectivity outcomes, indexed via resting state functional connectivity (rsFC). We conducted a systematic review and meta-analysis of rsFC as an outcome of mindfulness training (MT) relative to control, with the hypothesis that MT would increase cross-network connectivity between nodes of the Default Mode Network (DMN), Salience Network (SN), and Frontoparietal Control Network (FPCN) as a mechanism of internally-oriented attentional control. Texts were identified from the databases: MEDLINE/PubMed, ERIC, PSYCINFO, ProQuest, Scopus, and Web of Sciences; and were screened for inclusion based on experimental/quasi-experimental trial design and use of mindfulness-based training interventions. RsFC effects were extracted from twelve studies (mindfulness n  = 226; control n  = 204). Voxel-based meta-analysis revealed significantly greater rsFC (MT > control) between the left middle cingulate ( Hedge’s g  = .234, p  = 0.0288, I 2  = 15.87), located within the SN, and the posterior cingulate cortex, a focal hub of the DMN. Egger’s test for publication bias was nonsignificant, bias = 2.17, p  = 0.162. In support of our hypothesis, results suggest that MT targets internetwork (SN-DMN) connectivity implicated in the flexible control of internally-oriented attention.

In vivo targeted gene disruption is a powerful tool to study gene function. Thus far, two tools for genome editing in Aedes aegypti have been applied, zinc-finger nucleases (ZFN) and transcription activator-like effector nucleases (TALEN). As a promising alternative to ZFN and TALEN, which are difficult to produce and validate using standard molecular biological techniques, the clustered regularly interspaced short palindromic repeats/CRISPR-associated sequence 9 (CRISPR/Cas9) system has recently been discovered as a \"do-it-yourself\" genome editing tool. Here, we describe the use of CRISPR/Cas9 in the mosquito vector, Aedes aegypti. In a transgenic mosquito line expressing both Dsred and enhanced cyan fluorescent protein (ECFP) from the eye tissue-specific 3xP3 promoter in separated but tightly linked expression cassettes, we targeted the ECFP nucleotide sequence for disruption. When supplying the Cas9 enzyme and two sgRNAs targeting different regions of the ECFP gene as in vitro transcribed mRNAs for germline transformation, we recovered four different G1 pools (5.5% knockout efficiency) where individuals still expressed DsRed but no longer ECFP. PCR amplification, cloning, and sequencing of PCR amplicons revealed indels in the ECFP target gene ranging from 2-27 nucleotides. These results show for the first time that CRISPR/Cas9 mediated gene editing is achievable in Ae. aegypti, paving the way for further functional genomics related studies in this mosquito species.

The MITO-END3 trial compared carboplatin and paclitaxel (CP) with avelumab plus carboplatin and paclitaxel (CPA) as first-line treatment in endometrial cancer (EC) patients and demonstrated a significant interaction between avelumab response and mismatch repair status. To investigate prognostic/predictive biomarker, 29 MITO-END3-EC patients were evaluated at pretreatment (B1) and at the end of CP/CPA treatment (B2) for peripheral myeloid-derived suppressor cells (MDSC) and Tregs. At B2, effector Tregs frequency was significantly higher in patients treated with CPA as compared to CP ( p  = 0.038). Both treatments (CP/CPA) induced significant decrease in peripheral M-MDSC (− 5.41%) in TCGA 2-MSI-high as compared to TCGA-category 4 tumors ( p  = 0.004). In accordance, both treatments induced M-MDSCs (+ 5.34%) in MSS patients as compared to MSI-high patients ( p  = 0.001). Moreover, in a subgroup of patients, primary tumors were highly infiltrated by M-MDSCs in MSS as compared to MSI-high ECs. A post hoc analysis displayed higher frequency of M-MDSCs ( p  = 0.020) and lower frequency of CD4+ ( p  < 0.005) at pretreatment in EC patients as compared to healthy donors. In conclusion, the peripheral evaluation of MDSCs and Tregs correlated with molecular features in EC treated with CP/CPA and may add insights in identifying EC patients responder to first-line chemo/chemo-immunotherapy. Graphical abstract

The baculoviral chitinase (CHIA) and cathepsin (V-CATH) enzymes promote terminal insect host liquefaction, which aids viral progeny dissemination. Recombinant Autographa californica nucleopolyhedrovirus (AcMNPV)-derived viruses were previously generated with reprogrammed chiA transcription by replacing the native promoter with the AcMNPV polyhedrin (polh) or core protein (p6.9) promoter sequences, but of both these chiA-reprogrammed viruses lacked v-cath transcription and V-CATH enzymatic activity. Here, we report that dual p6.9/polh promoter reprogramming of the adjacent chiA/v-cath genes resulted in modulated temporal transcription of both genes without impacting infectious budded virus production. These promoter changes increased CHIA and V-CATH enzyme activities in infected Spodoptera frugiperda-derived cultured cells and Trichoplusia ni larvae. In addition, larvae infected with the dual reprogrammed virus had earlier mortalities and liquefaction. This recombinant baculovirus, lacking exogenous genomic elements and increased chiA/v-cath expression levels, may be desirable for and amenable to producing enhanced baculovirus-based biopesticides.

This paper addresses the critical gap in predicting the heat transfer coefficient during flow boiling in enhanced tubes, where the use of conventional correlations and predictive methods developed for smooth surfaces do not usually provide satisfactory results. For such purpose, a comprehensive database was collected from existing literature, including a wide range of operating conditions and enhanced tube geometries from several independent sources. The dataset includes mass flow rates spanning from 50 to 1000 kg/m 2 s, vapor qualities from the onset of boiling ( x =0.0) to the dry-out occurrence and beyond ( x =0.99), reduced pressures from 0.05 to 0.80, and tube diameters (measured up to the fin tip) from 0.7 to 11.9 mm, for a total amount of approximately 3000 data points. Existing flow boiling heat transfer coefficient predictive methods for enhanced tubes were implemented and tested with the present dataset, proving a limited accuracy for most of them mainly in case of testing beyond the specific parameter ranges they were developed for. Extrapolation frequently resulted in statistically poor or even non-physical outcomes. Several artificial neural network models were then developed, according to sensitivity analysis approach to look for potential input parameters and network structures. Specifically, two approaches were employed: a standard neural network model and a correlated informed neural network (CINN), integrating physical correlations into the network’s architecture, thus informing the model with physical principles that govern the heat transfer process. Despite a lower overall accuracy, the correlated informed neural network demonstrated superior reliability than standard one, resulting in an instrument to improve the accuracy of existing correlations.

Fibroblast growth factors (FGFs) are conserved among vertebrate and invertebrate animals and function in cell proliferation, cell differentiation, tissue repair, and embryonic development. A viral fibroblast growth factor (vFGF) homolog encoded by baculoviruses, a group of insect viruses, is involved in escape of baculoviruses from the insect midgut by stimulating basal lamina remodeling. This led us to investigate whether cellular FGF is involved in the escape of an arbovirus from mosquito midgut. In this study, the effects of manipulating FGF expression on Sindbis virus (SINV) replication and escape from the midgut of the mosquito vector Aedes aegypti were examined. RNAi-mediated silencing of either Ae. aegypti FGF (AeFGF) or FGF receptor (AeFGFR) expression reduced SINV replication following oral infection of Ae. aegypti mosquitoes. However, overexpression of baculovirus vFGF using recombinant SINV constructs had no effect on replication of these viruses in cultured mosquito or vertebrate cells, or in orally infected Ae. aegypti mosquitoes. We conclude that reducing FGF signaling decreases the ability of SINV to replicate in mosquitoes, but that overexpression of vFGF has no effect, possibly because endogenous FGF levels are already sufficient for optimal virus replication. These results support the hypothesis that FGF signaling, possibly by inducing remodeling of midgut basal lamina, is involved in arbovirus midgut escape following virus acquisition from a blood meal.

According to the new European policies aimed at the replacement of highly-pollutant greenhouse gases refrigerants, the scientific community has focused on new synthetic environmentally friendly substances to be employed in vapor compression cycles for the refrigeration and the air conditioning fields. On this regard, R450A is a new blend made up of R134a (42%) and R1234ze (58%), having a GWP equal to 604, and therefore represents an attractive solution as pure R134a substitute. In this paper, new flow boiling heat transfer and pressure drop data of R450A collected at the refrigeration lab of Federico II University of Naples are presented. The data refer to a horizontal stainless-steel tube having an internal diameter of 6.0 mm. The effects of mass flux (from 150 to 400 kg m −2 s −1 ), heat flux (from 10 to 20 kW m −2 ) and saturation temperature (from 30 to 50 °C) are presented and discussed, together with the assessment of the most quoted two-phase heat transfer and pressure drop prediction methods.

Most arthropod-borne and invertebrate viruses are orally ingested and commence infection in cells of the invertebrate intestine. Infection of secondary sites and eventual transmission to other hosts is hindered by basal lamina, a tightly interwoven and virus-impenetrable noncellular layer, lining the intestine and other organ cell layers. The mechanisms for viral escape across basal laminae are unknown. We describe an elegant mechanism mediated by a baculovirus-encoded fibroblast growth factor (vFGF) that signals a previously undescribed stepwise cascade of protease activation wherein matrix metalloproteases activate effector caspases, leading to remodeling of basal lamina lining tracheal cells associated with the intestine and culminating in the establishment of efficient systemic infections. Because FGFs coordinate diverse functions during development, metabolic processes, and tissue repair, it is plausible that the vFGF-mediated pathway described here is widely used during developmental and pathogenic processes that involve basal lamina remodeling.

The accurate analysis of any possible source of beam instability is mandatory for the design of a new particle accelerator, especially for high-current and ultra-low emittance synchrotrons. In the specific case of instabilities driven by the coupling between the charged particle beam and the electromagnetic field excited by the beam itself, the corresponding effect is estimated through the beam coupling impedance. The modeling of this effect is essential to perform a rigorous evaluation of the coupling impedance budget able to account for all devices present in the entire machine. To deal with this problem, this paper focuses on the estimation of the contribution of the joints lying between the different vacuum chamber sections, by performing a comparative numerical analysis that takes into account different aperture gaps between the flanges. The results point out the criticality of many small-impedance contributions that, added together, must be lower than a predefined impedance threshold.