bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effects of Disease-Modifying Therapies on Oxidative Stress in Patients With Relapsing-Remitting Multiple Sclerosis
Authors: Topic Aleksandra , Vasic Marija , Markovic Bojan , Milinkovic Neda , Dincic Evica
Published: September 2022

Objective

Oxidative stress (OS) has a role in the pathogenesis and progression of multiple sclerosis. The effects of disease-modifying therapies (DMTs) on OS are unclear. We aimed to explore the association between DMTs and OS in patients with relapsing-remitting multiple sclerosis (RRMS).

Methods

The study conducted in 167 patients (102 received and 65 not received the DMTs). The DMTs included interferon beta-1a (n = 15), interferon beta-1b (n = 20), glatiramer acetate (n = 10), and sphingosine-1-phosphate receptor modulators (n = 57). Oxidative stress assessed by total antioxidant status (TAS) and total oxidant status (TOS) (determined by spectrophotometric method), oxidative index (OSI was calculated), and urinary 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG/creatinine was determined by high-performance liquid chromatography and tandem mass spectrometry). Patients were classified by Multiple Sclerosis Severity Score (MSSS) to mild/moderate (MSSS, <6.7) and severe (MSSS, >6.7).

Results

Disease-modifying therapies are associated with increased TAS, decreased TOS, OSI, and 8-oxodG/creatinine. Regardless of therapy, women had a less favorable redox status (lower TAS, higher TOS and OSI). Patients with MSSS>6.7 and without DMTs had higher OSI than patients who received DMTs. Women with MSSS>6.7 without DMTs had lower TAS than women with DMTs, whereas in the same stage of MS, men without DMTs had higher TOS than patients with DMTs. Women with MSSS<6.7 and with DMTs had lower 8-oxodG/creatinine compared with those without DMT therapy.

Conclusions

The antioxidant effects of DMTs were evidenced in this study. The gender-related effects of DMTs on the OS imply the personalized antioxidant pharmacotherapy, especially for the women. The OS biomarkers have a potential as the prognostic for the assessment of DMTs outcomes in patients with RRMS.
Aspects of flow variability and spatial context predict temporal beta diversity in river metacommunities
Authors: Saffarinia P. , Conway R. , Anderson K.E
Published: September 2022

River catchments are dynamic networks that contain multiple levels of spatial and temporal complexity. Benthic macroinvertebrates are key indicator taxa throughout catchments and beta diversity has been used as a metric to explore determinants of community composition at the catchment scale. Commonly explored drivers of beta diversity include environmental and spatial variables such as flow, temperature, and spatial distance. While factors influencing spatial beta diversity have been explored, factors explaining temporal beta diversity have been understudied. Temporal beta diversity is predicted to also be important since community assembly mechanisms are not stable over time, and more studies are needed to determine which factors most strongly determine temporal beta diversity patterns.

We investigated the effects of local environmental variables, flow variability, and spatial context on temporal beta-diversity using a large, publicly available biomonitoring dataset from river networks in California. Data included benthic macroinvertebrate community composition and environmental data from multiple locations and years, allowing us to explore temporal changes in these communities as a function of site-specific environmental and spatial factors. Associated gage data were used to calculate hydrograph metrics and contextualize the flow regime at each location over long timescales. We then used beta regression to model the relationship between benthic macroinvertebrate temporal beta-diversity, environmental variables, flow regimes, and spatial network context.

Flow and spatial catchment-related predictors were the strongest predictors of temporal beta diversity, while changes in environmental variables were much weaker. Channel slope, drainage density, and upstream catchment area were the most significant spatial factors. Channel slope showed a negative relationship with temporal beta diversity, while drainage density and upstream catchment area showed positive ones. Temporal beta diversity was also higher when the rate and magnitude of rises and falls in flow was higher in the hydrograph as well as when the number of zero-flow days and the duration of flow rises and falls was higher.

Overall, our results indicate that temporal beta diversity of freshwater benthic macroinvertebrates is shaped by both long-term hydrological context and spatial context, and that these factors may serve as better predictors of long term community variability than variability in point estimates of environmental measurements. Flow regimes and spatial metrics may provide more environmental context than point-estimate environmental measurements, as the latter may not accurately capture the dynamic conditions that drive variability in metacommunity responses.

Our study supports the need for biomonitoring efforts at long spatial and temporal timescales, and highlights the need to consider metacommunity change in the management of freshwater systems.
Natural variation in codon bias and mRNA folding strength interact synergistically to modify protein expression in Saccharomyces cerevisiae
Authors: Wienecke Anastacia N. , Barry Margaret L. , Pollard Daniel A.
Published: September 2022

Codon bias and mRNA folding strength (mF) are hypothesized molecular mechanisms by which polymorphisms in genes modify protein expression. Natural patterns of codon bias and mF across genes as well as effects of altering codon bias and mF suggest the influence of these two mechanisms may vary depending on the specific location of polymorphisms within a transcript. Despite the central role codon bias and mF may play in natural trait variation within populations, systematic studies of how polymorphic codon bias and mF relate to protein expression variation are lacking. To address this need, we analyzed genomic, transcriptomic, and proteomic data for 22 Saccharomyces cerevisiae isolates, estimated protein accumulation for each allele of 1620 genes as the log of protein molecules per RNA molecule (logPPR), and built linear mixed effects models associating allelic variation in codon bias and mF with allelic variation in logPPR. We found codon bias and mF interact synergistically in a positive association with logPPR and this interaction explains almost all the effect of codon bias and mF. We examined how the locations of polymorphisms within transcripts influence their effects and found that codon bias primarily acts through polymorphisms in domain encoding and 3’ coding sequences while mF acts most significantly through coding sequences with weaker effects from UTRs. Our results present the most comprehensive characterization to date of how polymorphisms in transcripts influence protein expression.
Identifying opportunities for high resolution pesticide usage data to improve the efficiency of endangered species pesticide risk assessment
Authors: Eikenberry Steffen E. , Iacona Gwen , Murphy Erin L. , Watson Greg , Gerber Leah R.
Published: September 2022

The US pesticide registration and review process requires regular re-assessment of the risk of pesticide use, including risk to species listed under the Endangered Species Act (ESA). Yet, current methods for assessment were not designed to assess threats that could involve hundreds of pesticides potentially impacting multiple species across a continent. Thus, many pesticides remain on the market without complete review under ESA. A promising approach to address this challenge calls for the use of high-resolution data in the spatial analyses used to determine the likelihood of adverse effect. However, such data are rare, and implementing data collection initiatives are difficult and expensive. Here we examine the extent to which increased data resolution could result in significant gains in efficiency to the pesticide risk assessment process. To do so, we employ a modified value-of-information (VOI) approach. By using data available only in California, we found that high resolution data increased the number of species deemed not likely to be adversely affected by pesticides from less than 5% to nearly 50%. Across the contiguous US, we predicted that 48% of species would be deemed not likely to be adversely affected using high resolution data, compared to 20% without. However, if such data were available in just 11 states, 68% of the available gains in efficiency could be obtained. Therefore, a focused collection or release of high-resolution pesticide usage data could expedite pesticide risk assessment and reduce endangered species’ risk of pesticide impacts.

Significance

Regulation of environmental risk must balance avoidance of harm with assessment efficiency. The current pesticide registration and review process in the U.S. is generally considered ineffective in assessing impact on species listed under the Endangered Species Act, due to the vast scale of the problem. We assessed the value of using high resolution pesticide usage data in the risk assessment process to identify cost-effective opportunities to rapidly improve this assessment process and ensure that ESA listed species are protected while accounting for agricultural production. Our results suggest that using existing high-resolution data in California and collection of such information from 11 other states could reduce the risk assessment burden across the contiguous U.S. by one-quarter.
Neogene climatic fluctuations and poor connectivity with the centres of diversity shaped the Western Palearctic net-winged beetle fauna
Authors: Motyka Michal , Kusy Dominik , Bilkova Renata , Bocak Ladislav
Published: September 2022

Only twenty-two net-winged beetle species (Elateroidea: Lycidae) are known from the Western Palearctic region (WPR), i.e., less than 0.5% of the global lycid diversity and much fewer than from the similar latitudes of East Asia or Northern America. We use the comprehensive distribution data and the molecular phylogeny of ∼400 world lycids, including fourteen European species, to provide a new perspective for understanding the structure and evolution of this group in the WPR. All Mediterranean species represent deeply rooted lineages with relatives in Eastern Asia. These species occur in relictual ranges close to the family’s Pleistocene refugial edge. The phylogeny points to the loss of biological connection with East Asia since the Mid Miocene. A third of WPR species is widespread in Central and Northern Europe, reaching Eastern Asia, some of them possibly younger elements of the European fauna. Unlike relatively high diversity in the Eocene amber, the extant net-winged beetles represent a small fraction of elateroid diversity in the WPR and are generally rare. Therefore, we assume that most WPR species are relics trapped in Mediterranean refugia since the onset of the Plio-Pleistocene cooling and are critically endangered by the ongoing loss of suitable habitats.
Cyanotoxins accumulate in Lake St. Clair fish yet their fillets are safe to eat
Authors: Shahmohamadloo René S. , Bhavsar Satyendra P. , Almirall Xavier Ortiz , Marklevitz Stephen A. C. , Rudman Seth M. , Sibley Paul K.
Published: September 2022

Consuming fish exposed to cyanobacterial harmful algal blooms (HABs) may be a major route of microcystin toxin exposure to humans. However, it remains unknown whether fish can accumulate and retain microcystins temporally in waterbodies with recurring seasonal HABs, particularly before and after a HAB event when fishing is active. We conducted a field study on Largemouth Bass, Northern Pike, Smallmouth Bass, Rock Bass, Walleye, White Bass, and Yellow Perch to assess the human health risks to microcystin toxicity via fish consumption. We collected 124 fish in 2016 and 2018 from Lake St. Clair, a large freshwater ecosystem in the North American Great Lakes that is actively fished pre- and post-HAB periods. Muscles were analyzed using the MMPB Lemieux Oxidation method for total microcystins, which was used to perform a human health risk assessment for comparison against fish consumption advisory benchmarks available for Lake St. Clair. From this collection 35 fish livers were additionally extracted to confirm the presence of microcystins. Microcystins were detected in all livers at widely varying concentrations (1-1,500 ng g-1ww), suggesting HABs are an underappreciated and pervasive stressor to fish populations. Conversely, microcystin levels were consistently low in muscles (0-15 ng g-1ww) and presented negligible risk, empirically supporting that fillets may be safely consumed before and after HAB events following fish consumption advisories.
Embryonic Vitamin D Deficiency Programs Hematopoietic Stem Cells to Induce Type 2 Diabetes
Authors: Oh Jisu , Riek Amy E. , Bauerle Kevin T. , Dusso Adriana , McNerney Kyle P. , Barve Ruteja A. , Darwech Isra , Sprague Jennifer , Moynihan Clare , Zhang Rong M , Wang Ting , Xing Xiaoyun , Li Daofeng , Head Richard D. , Bambouskova Monika , Mrad Marguerite , Collins Alejandro , Sands Mark S. , Bernal-Mizrachi Carlos
Published: September 2022

Environmental factors may alter the fetal genome to cause metabolic diseases. It is unknown whether embryonic immune cell programming impacts the risk of type 2 diabetes in later life. We demonstrate that transplantation of fetal hematopoietic stem cells (HSCs) made vitamin D deficient in utero induces diabetes in vitamin D-sufficient mice. Vitamin D deficiency epigenetically suppresses Jarid2 expression and activates the Mef2/PGC1a pathway in HSCs, which persists in recipient bone marrow, resulting in adipose macrophage infiltration. These macrophages secrete miR106-5p, which promotes adipose insulin resistance by repressing PIK3 catalytic subunit alpha and AKT signaling. Vitamin D-deficient monocytes from human cord blood have comparable Jarid2/Mef2/PGC1a expression changes and secrete miR-106b-5p, causing adipocyte insulin resistance. These findings suggest that vitamin D deficiency during development has epigenetic consequences impacting the systemic metabolic milieu.
Phylogeny-aware linear B-cell epitope predictor detects candidate targets for specific immune responses to Monkeypox virus
Authors: Campelo Felipe , Reis-Cunha João , Ashford Jodie , Ekárt Anikó , Lobo Francisco P.
Published: September 2022

Monkeypox is a disease caused by the Monkeypox virus (MPXV), a double-stranded DNA virus from genusOrthopoxvirusunder familyPoxviridae, that has recently emerged as a global health threat after decades of local outbreaks in Central and Western Africa. Effective epidemiological control against this disease requires the development of cheaper, faster diagnostic tools to monitor its spread, including antigen and serological testing. There is, however, little available information about MPXV epitopes, particularly those that would be effective in discriminating between MPXV infections and those by other virus from the same family. We used the available data from the Immune Epitope Database (IEDB) to generate and validate a predictive model optimised for detecting linear B-cell epitopes (LBCEs) fromOrthopoxvirus, based on a phylogeny-aware data selection strategy. By coupling this predictive approach with conservation and similarity analyses, we identified nine specific peptides from MPXV that are likely to represent distinctive LBCEs for the diagnostic of Monkeypox infections, including the independent detection of a known epitope experimentally characterised as a potential specific diagnostic target for MPXV. The results obtained indicate ability of the proposed pipeline to uncover promising targets for the development of cheaper, more specific diagnostic tests for this emerging viral disease. A full reproducibility package (including code, data, and outputs) is available athttps://doi.org/10.5281/zenodo.7838331.
Transcriptome-wide characterization of piRNAs during the developmental process of European honey bee larval guts
Authors: Xu Ya-Jing , Long Qi , Fan Xiao-Xue , Ye Ya-Ping , Zhang Kai-Yao , Zhang Jia-Xin , Zhao Hao-Dong , Yao Yu-Tong , Ji Ting , Lin Zhe-Guang , Fu Zhong-Min , Chen Da-Fu , Guo Rui
Published: September 2022

piRNAs play pivotal roles in suppressing transposons, maintaining genome stability, regulating gene expression, and modulating development and immunity. However, there are few piRNA-associated studies on honey bee, and the regulatory role of piRNAs in the development of bee guts is largely unknown. In this current work, the differential expression pattern of piRNAs during the developmental process of the European honey bee (Apis mellifera) was analyzed, and target prediction of differentially expressed piRNAs (DEpiRNAs) was then conducted, followed by investigation of regulatory networks and the potential function of DEpiRNAs in regulating larval gut development. Here, a total of 843 piRNAs were identified in the larval guts ofA. mellifera; among these, 764 piRNAs were shared by 4- (Am4 group), 5- (Am5 group), and 6-day-old (Am6 group) larval guts, while 11, 67, and 1, respectively, were unique. The first base of piRNAs in each group had a cytosine (C) bias. Additionally, 61 up-regulated and 17 down-regulated piR-NAs were identified in the Am4 vs. Am5 comparison group, further targeting 9, 983 genes, which were involved in 50 GO terms and 142 pathways, while two up-regulated and five down-regulated piRNAs were detected in the Am5 vs. Am6 comparison group, further targeting 1, 936 genes, which were engaged in 41 functional terms and 101 pathways. piR-ame-742536 and piR-ame-856650 in the Am4 vs. Am5 comparison group as well as piR-ame-592661 and piR-ame-31653 in the Am5 vs. Am6 comparison group were found to link to the highest number of targets. Further analysis indicated that targets of DEpiRNAs in these two comparison groups were seven development-associated signaling pathways such as Hippo and Notch signaling pathways, seven immune-associated pathways including endocytosis and the Jak/STAT signaling pathway, and three energy metabolism pathways, namely sulfur metabolism, nitrogen metabolism, and oxidative phosphorylation. Moreover, the expression trends of five randomly selected DEpiRNAs were verified based on stem-loop RT-PCR and RT-qPCR. These results were suggestive of the overall alteration of piRNAs during the larval developmental process and demonstrated that DEpiRNAs potentially modulate development-, immune-, and energy metabolism-associated pathways by regulating expression of corresponding genes via target binding, further affecting the development ofA. melliferalarval guts. Our data offer novel insights into the development of bee guts and lay a basis for clarifying the developmental mechanism underlying the larval guts of European honey bee.
You Will Grasp Again: A Direct Spinal Cord/Computer Interface with the Spared Motor Neurons Restores the Dexterous Control of the Paralyzed Hand after Chronic Spinal Cord Injury
Authors: Oliveira Daniela Souza , Ponfick Matthias , Braun Dominik I. , Osswald Marius , Sierotowicz Marek , Chatterjee Satyaki , Weber Douglas , Eskofier Bjoern , Castellini Claudio , Farina Dario , Kinfe Thomas Mehari , Vecchio Alessandro Del
Published: September 2022

The paralysis of the muscles controlling the hand dramatically limits the quality of life of individuals living with spinal cord injury (SCI). Here, we present a non-invasive neural interface technology that will change the lives of individuals living with cervical SCI (C4-C6). We demonstrate that eight motor- and sensory-complete SCI individuals (C5-C6, n = 7; C4, n = 1) are still able to task-modulate in real-time the activity of populations of spinal motor neurons with spared corticospinal pathways. In all tested patients, we identified groups of motor units under voluntary control that encoded a variety of hand movements. The motor unit discharges were mapped into more than 10 degrees of freedom, ranging from grasping to individual hand digit flexions and extensions. We then mapped the neural dynamics into a real-time controlled virtual hand. The patients were able to match the cue hand posture by proportionally controlling four degrees of freedom (opening and closing the hand and index flexion/extension). These results demonstrate that wearable muscle sensors provide access to voluntarily controlled neural activity in complete cervical SCI individuals.
The class XIV myosin ofToxoplasma gondii, TgMyoA, is druggable in an animal model of infection
Authors: Kelsen Anne , Kent Robyn S , Snyder Anne K , Wehri Eddie , Bishop Stephen J , Stadler Rachel V , Powell Cameron , di Genova Bruno Martorelli , Rompikuntal Pramod K , Boulanger Martin J , Warshaw David M , Westwood Nicholas J , Schaletzky Julia , Ward Gary E
Published: September 2022

Toxoplasma gondiiis a widespread apicomplexan parasite that can cause severe disease in its human hosts. The ability ofT. gondiiand other apicomplexan parasites to invade into, egress from, and move between cells of the hosts they infect is critical to parasite virulence and disease progression. An unusual and highly conserved parasite myosin motor (TgMyoA) plays a central role inT. gondiimotility. The goal of this work was to test whether pharmacological inhibition of TgMyoA can alter disease progression in an animal model of infection. To this end, we sought to identify small molecule inhibitors of TgMyoA by screening a collection of 50,000 structurally diverse small molecules for inhibitors of the recombinant motors actin-activated ATPase activity. The top hit to emerge from the screen, KNX-002, inhibited TgMyoA with little to no effect on any of the vertebrate myosins tested. KNX-002 was also active against parasites, inhibiting parasite motility and growth in culture in a dose-dependent manner. We used chemical mutagenesis, selection in KNX-002, and targeted sequencing to identify a mutation in TgMyoA (T130A) that renders the recombinant motor less sensitive to compound. Compared to wild-type parasites, parasites expressing the T130A mutation showed reduced sensitivity to KNX-002 in motility and growth assays, confirming TgMyoA as a biologically relevant target of KNX-002. Finally, KNX-002 was shown to slow disease progression in mice infected with wild-type parasites, but not parasites expressing the resistance-conferring TgMyoA T130A mutation. These data demonstrate the specificity of KNX-002 for TgMyoA, bothin vitroandin vivo, and validate TgMyoA as a druggable target for toxoplasmosis. Since TgMyoA is essential for virulence, conserved in apicomplexan parasites, and distinctly different from the myosins found in humans, pharmacological inhibition of MyoA offers a promising new approach to treating the devastating diseases caused byT. gondiiand other apicomplexan parasites.
Metataxonomic insights in the distribution ofLactobacillaceaein foods and food environments
Authors: Parente Eugenio , Zotta Teresa , Giavalisco Marilisa , Ricciardi Annamaria
Published: September 2022

Members of the familyLactobacillaceae, which now includes species formerly belonging to the generaLactobacillusandPediococcus, but alsoLeuconostocaceae, are of foremost importance in food fermentations and spoilage, but also as components of animal and human microbiota and as potentially pathogenic microorganisms. Knowledge of the ecological distribution of a given species and genus is important, among other things, for the inclusion in lists of microorganisms with a Qualified Presumption of Safety or with beneficial use. The objective of this work is to use the data in FoodMicrobionet database to obtain quantitative insights (in terms of both abundance and prevalence) on the distribution of these bacteria in foods and food environments.

We first explored the reliability of taxonomic assignments using the SILVA v138.1 reference database with full length and partial sequences of the 16S rRNA gene for type strain sequences. Full length 16S rRNA gene sequences allow a reasonably good classification at the genus and species level in phylogenetic trees but shorter sequences (V1-V3, V3-V4, V4) perform much worse, with type strains of many species sharing identical V4 and V3-V4 sequences. Taxonomic assignment at the genus level of 16S rRNA genes sequences and the SILVA v138.1 reference database can be done for almost all genera of the familyLactobacillaceaewith a high degree of confidence for full length sequences, and with a satisfactory level of accuracy for the V1-V3 regions. Results for the V3-V4 and V4 region are still acceptable but significantly worse. Taxonomic assignment at the species level for sequences for the V1-V3, V3-V4, V4 regions of the 16S rRNA gene of members of the familyLactobacillaceaeis hardly possible and, even for full length sequences, and only 49.9% of the type strain sequences can be unambiguously assigned to species.

We then used the FoodMicrobionet database to evaluate the prevalence and abundance ofLactobacillaceaein food samples and in food related environments. Generalist and specialist genera were clearly evident. The ecological distribution of several genera was confirmed and insights on the distribution and potential origin of rare genera (Dellaglioa, Holzapfelia, Schleiferilactobacillus) were obtained.

We also found that combining Amplicon Sequence Variants from different studies is indeed possible, but provides little additional information, even when strict criteria are used for the filtering of sequences.
Quantifying the bioavailable energy in an ancient hydrothermal vent on Mars and a modern Earth-based analogue
Authors: Rucker Holly R. , Ely Tucker D. , LaRowe Douglas E. , Giovannelli Donato , Price Roy E.
Published: September 2022

Putative alkaline hydrothermal systems on Noachian Mars were potentially habitable environments for microorganisms. However, the types of reactions that could have fueled microbial life in such systems and the amount of energy available from them have not been quantitatively constrained. In this study, we use thermodynamic modeling to calculate which catabolic reactions could have supported ancient life in a saponite-precipitating hydrothermal vent system in the Eridania basin on Mars. To further evaluate what this could mean for microbial life, we evaluated the energy potential of an analogue site in Iceland, the Strytan Hydrothermal Field (SHF). Results show that out of the 85 relevant redox reactions that were considered, the highest energy-yielding reactions in the Eridania hydrothermal system were dominated by methane formation. By contrast, Gibbs energy calculations carried out for Strytan indicate that the most energetically favorable reactions are CO2 and O2 reduction coupled to H2 oxidation. In particular, our calculations indicate that an ancient hydrothermal system within the Eridania basin could have been a habitable environment for methanogens using NH4+ as an electron acceptor. Differences in Gibbs energies between the two systems were largely determined by oxygen – its presence on Earth and absence on Mars. However, Strytan can serve as a useful analogue for Eridania when studying methane producing reactions that do not involve O2.
The protein phosphatases MoPtc1 and MoPtc2 are induced during pathogen-host interactions and play synergistic roles in regulating MAPK pathways inMagnaporthe oryzae
Authors: Anjago Wilfred M. , Biregeya Jules , Shi Mingyue , Chen Yixiao , Wang Yupeng , Chen Meilian , Aron Osakina , Norvienyeku Justice , Yu Wenyi , Wang Zonghua , Dongmei Zhang
Published: September 2022

Reversible protein phosphorylation is essential in cellular signal transduction. The rice blast fungusMagnaporthe oryzae, contains six putative type 2c protein phosphatases namely; MoPtc1, MoPtc2, MoPtc5, MoPtc6, MoPtc7 and MoPtc8 respectively. In this study, we carried out transcription expression analysis and found that MoPtc1, MoPtc2 and MoPtc7 are significantly induced during pathogen-host interactions. Subsequent deletions of MoPtc1 or MoPtc2 not only resulted in increased sensitivity to cell wall stress mediated by Congo red but also increased phosphorylation of Mps1-MAPK. By immunoblot analysis, we found that deletion of both MoPtc1 and MoPtc2 resulted in overstimulation of both the HOG1 and Pmk1 pathways inM. oryzae. We also demonstrate that MoPtc1 is recruited directly to Osm1 by the adaptor protein MoNbp2 to inactivate the Osm1 during hypoosmotic stress unlike in budding yeast. Finally, we show that type 2c protein phosphatases are localized in different cellular compartments in the life cycle ofMagnaporthe oryzae. Taken together type 2C protein phosphatases MoPtc1 and MoPtc2 play synergistic roles in regulating MAPK signaling pathways inM. oryzae. This work expands our understanding of the MAPK signaling regulation circuits inM. oryzaeand the essential roles of type 2C phosphatases in fine-tuning phosphorylation levels of MAPK during fungal development.
Optogenetic induction of chronic glucocorticoid exposure in early-life impairs stress-response in larval zebrafish
Authors: Nagpal Jatin , Eachus Helen , Lityagina Olga , Ryu Soojin
Published: September 2022

Organisms respond to stressors through a coordinated set of physiological and behavioural responses. Zebrafish provides an opportunity to study conserved mechanisms underlying the stress-response that is regulated largely by the neuroendocrine Hypothalamus-Pituitary-Adrenal/Interrenal (HPA) axis, with glucocorticoids (GC) as the final effector. In this study, we evaluated the effect of chronically active GC signalling in early life on the baseline and stress evoked GC(cortisol) levels in larval zebrafish. To this end, we employed an optogenetic actuator, Beggiatoa photoactivated adenylyl cyclase, expressed in the interrenal cells of zebrafish and demonstrate that its chronic activation leads to hypercortisolaemia and dampens the acute-stress evoked cortisol levels, across a variety of stressor modalities during early life. This blunting of stress-response, a phenotype reported by many studies to be observed in human subjects exposed to early-life trauma, was conserved in ontogeny at a later developmental stage. Furthermore, we observe a strong reduction of proopiomelanocortin (POMC)-expressing cells in the pituitary as well as global upregulation of FKBP5 gene expression, impinging on the negative feedback regulation elicited by elevated cortisol levels. Going forward, we propose that this model can be leveraged to tease apart the mechanisms underlying developmental programming of HPA axis by early-life stress and its implications for vulnerability and resilience to stress in adulthood.
Clomipramine inhibits dynamin GTPase activity by L-α-phosphatidyl-L-serine stimulation
Authors: Miyoshi Hiroshi , Otomo Masahiro , Takahashi Kiyofumi
Published: September 2022

Three dynamin isoforms play critical roles in clathrin-dependent endocytosis. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters host cellsviaclathrin-dependent endocytosis. We previously reported that 3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)-N,N-dimethylpropan-1-amine (clomipramine) inhibits the GTPase activity of dynamin 1, which is in mainly neuron. Therefore, we investigated whether clomipramine inhibits the activity of other dynamin isoforms in this study. We found that, similar to its inhibitory effect on dynamin 1, clomipramine inhibited the L-α-phosphatidyl-L-serine-stimulated GTPase activity of dynamin 2, which is expressed ubiquitously, and dynamin 3, which is expressed in the lung. Inhibition of GTPase activity raises the possibility that clomipramine can suppress SARS-CoV-2 entry into host cells.

Graphical Abstract
Involvement of epithelial-mesenchymal transition genes in small cell lung cancer phenotypic plasticity
Authors: Groves Sarah M. , Panchy Nicholas , Tyson Darren R. , Harris Leonard A. , Quaranta Vito , Hong Tian
Published: September 2022

Small cell lung cancer (SCLC) is an aggressive cancer recalcitrant to treatment, arising predominantly from epithelial pulmonary neuroendocrine (NE) cells. Intra-tumor heterogeneity plays critical roles in SCLC disease progression, metastasis and treatment resistance. At least five transcriptional SCLC NE and non-NE cell subtypes were recently defined by gene expression signatures. Transition from NE to non-NE cell states and cooperation between subtypes within a tumor likely contribute to SCLC progression by mechanisms of adaptation to perturbations. Therefore, gene regulatory programs distinguishing SCLC subtypes or promoting transitions are of great interest. Here, we systematically analyze the relationship between SCLC NE/non-NE transition and epithelial to mesenchymal transition (EMT)—a well-studied cellular process contributing to cancer invasiveness and resistance—using multiple transcriptome datasets from SCLC mouse tumor models, human cancer cell lines and tumor samples. The NE SCLC-A2 subtype maps to the epithelial state. In contrast, SCLC-A and SCLC-N (NE) map to a mesenchymal state (M1) that is distinct from the non-NE mesenchymal state (M2). The correspondence between SCLC subtypes and the EMT program paves the way for further work to understand gene regulatory mechanisms of SCLC tumor plasticity with applicability to other cancer types.
Efficacy and safety of acupuncture for postpartum hypogalactia: Protocol for a systematic review and meta-analysis
Authors: Bao Qiong-Nan , Zhou Yuan-Fang , Yin Zi-Han , Qiu-Bi  , Zhao Hong-Bin , Zhang Zhen-Yong , Liang Fan-Rong
Published: September 2022

Introduction

Breast milk is recognised as the best natural food for neonates, but many women experience postpartum hypogalactia (PH). Randomised trials have found that acupuncture exert therapeutic effect on women with PH. However, systematic reviews on the efficacy and safety of acupuncture are still lacking; therefore, this systematic review aims to evaluate the efficacy and safety of acupuncture for PH.

Methods and analysis

Eight English databases (PubMed, Cochrane Library, MEDLINE, EMBASE, EBSCO, Scopus, Ovid, Web of Science) and four Chinese databases (China National Knowledge Infrastructure, Wan-Fang, Chinese Biomedical Literature, Chinese Scientific Journal) will be systematically searched from their establishment to 1 September 2022. Randomised controlled trials (RCTs) of the efficacy of acupuncture for PH will be reviewed. The study selection, data extraction, and research quality evaluation will be conducted independently by two reviewers. The primary outcome is the change in serum prolactin level from baseline to the end of treatment. Secondary results include milk secretion volume, total effectiveness rate, degree of mammary fullness, rate of exclusive breastfeeding, infant weight gain, and adverse events. A meta-analysis will be performed using RevMan V.5.4 statistical software. Otherwise, a descriptive analysis will be conducted. The risk of bias will be assessed using the revised Cochrane risk-of-bias tool.

Ethics and dissemination

This systematic review protocol does not require ethical approval because it does not include private information/data of the participants. This article will be published in peer-reviewed journals.

PROSPERO registration number

CRD42022351849

Strengths and limitations of this study

This study will be the first systematic review to evaluate the efficacy and safety of acupuncture for PH by including available clinical trials that have been published in the past.

The quality of the included trials will be assessed using the Revised Cochrane Risk of Bias Tool (RoB2) for Randomised Trials.

This study will provide more reliable evidence for clinical management because most RCTs on acupuncture for PH have small sample sizes.

This study will include only English and Chinese trials, which may lead to missing studies in other languages.
Effects of social determinants of health on obesity among urban women of reproductive age
Authors: Amugsi Dickson A , Dimbuene Zacharie T.
Published: September 2022

Background

Obesity (body mass index greater than or equal to 30kg/m2) is a major global public health problem. It is spreading very fast in low- and middle-income countries and has reached world record levels in some of them. In Ghana, it has increased by over 65% among urban women in the past three decades. This study investigated the effects of social determinants of health on obesity among women in urban Ghana.

Methods

The study analysed the Ghana demographic and health survey data. These are nationally representative data collective every five years across low- and middle-income countries. A total of 1,204 urban women were included in the analysis. The outcome variable of interest was body mass index. We used logistic regression to model the effects of the various social determinants of health on obesity.

Results

The results showed that 40% (95% confidence interval (CI)=25.4, 57.0) and 36.7% (95% CI=25.6, 49.3) of women who had higher education and those whose partners had higher education suffered from obesity, respectively. Women living in rich households had a five times higher prevalence of obesity than those in poor households (28.8% vs 5.7%). Further, 33.4% (95% CI=18.5, 19.3) of women who occupied managerial positions were obese. The results from the multivariable logistic regression analysis suggested that compared to women in poor households, those in rich households were 3.4 times (95% CI=1.31, 8.97) more likely to suffer from obesity. Women whose main occupation was agriculture were 81% (aOR=0.19; 95% CI=0.034, 0.99) less likely to suffer from obesity than those with no occupation.

Conclusions

The results suggest that the various SDHs significantly influence women’s obesity. Women and partner education levels, occupying a managerial position, and living in rich households increase the risk of obesity. Interventions to address the rising obesity in urban Ghana should have specific packages targeted at these sub-groups.
High serum uric acid levels are associated with worse cognitive performance: A cross-sectional study
Authors: Khaled Yousef , Abdelhamid Aya A. , Al-Mazroey Hissa , Almannai Abdulrahman K. , Fetais Sara , Al-Srami Aisha S. , Ahmed Shaima , Al-Hajri Noora , Chivese Tawanda , Djouhri Laiche
Published: September 2022

(1)

Background

The association between raised serum uric acid and cognitive dysfunction remains a debated issue. In the present study, we investigated whether serum uric acid is associated with cognitive performance in a cohort of healthy individuals in Qatar;

(2)

Methods

We conducted a cross-sectional study on a cohort of individuals aged 40 to 80 years old, without a diagnosis of dementia, schizophrenia, and stroke, who participated in Qatar Biobank. Cognitive performance was assessed using the CANTAB’s paired episodic memory test and reaction time test. The participants were divided into two groups, one group with a normal serum uric acid level (<350 μmol/l) and the other with high serum uric acid levels (>350 μmol/l). Two multivariable linear regression models were applied to determine the association between serum uric acid and memory test performance score and between serum uric acid and reaction time test performance score;

(3)

Results

A total of 996 individuals with median age 48.0 years, IQR: (44.5, 54.0), of which 48.2% were male, were included. After adjusted multivariable linear regression, high serum uric acid levels were strongly associated with poor performance in the paired episodic memory test (beta -6.25, 95%CI - 10.65 to -1.84, p= 0.006). However, after adjusted multivariable linear regression, we found no significant association between high serum uric acid and performance in the reaction time test (beta - 13.24, 95%CI -138.77 to 112.29, p= 0.836,);

(4)

Conclusions

In a cohort of healthy individuals in Qatar, high serum uric acid levels are associated with worse performance in visual memory and new learning domains of cognitive function but no significant effect on processing speed function.
Relationship between neurochemical concentrations and neurofunctional measures in late-onset GM2 gangliosidosis
Authors: Rangaprakash D , Weerasekera Akila , Rowe Olivia E , Stephen Christopher D , Eichler Florian S , Barry Robert L , Ratai Eva-Maria
Published: September 2022

Magnetic resonance spectroscopy (MRS) and functional MRI (fMRI), related through common biophysical bases, provide complementary information about brain function. The link between MRS and fMRI measures is of interest, especially in the ultra-rare, metabolic disease late-onset GM2 gangliosidosis (LOGG). Imaging studies on LOGG have been few and far between, with cerebellar atrophy and neurochemical impairments being the most prominent findings. However, it remains unknown as to how these neurochemical aberrations relate to neurofunctional characteristics. The goal of this study (7 LOGG, 7 age/sex matched controls) was to assess the relationship between MRS concentrations and fMRI measures derived from the same MRS ROI (cerebellum, thalamus, precuneus) in LOGG. To quantify the communication between MRS regions and rest of the brain, we employed graph measures estimated from resting-state fMRI functional connectivity. We found that one such measure, local efficiency, which quantifies the aggregate relationship between a MRS region and rest of the brain, was significantly associated with N-acetylaspartate (NAA) in the cerebellum and thalamus (p<0.05, FDR corrected). Poorer neuronal health, neuronal loss (NAA), and neuroinflammation (myo-inositol) were related to poorer cerebellum-brain communication. Likewise, reduced thalamus-brain communication was also associated with poorer neuronal health and longer disease duration (p=0.002). These findings hint at a model of impaired neurochemical concentrations in these regions, leading to aberrant communication between them and rest of the brain, which may exacerbate disease progression. Future research must replicate these findings in larger cohorts, and further investigate such abnormalities in the cerebellum, thalamus and precuneus in this ultra-rare neurological disease.
Sustainable Development Goals: a review of SDG 12.3 in food supply chain literature
Authors: Jacob-John Jubin , D'Souza Clare , Marjoribanks Timothy , Singaraju Stephen
Published: September 2022

Purpose

Food Loss and Waste (FLW), a result of non-sustainable consumption and production, has significant socio-environmental impacts and is addressed in the United Nation's Sustainable Development Goal (SDG) 12.3. To address current research on FLW and SDG 12.3, the authors aim to evidence the current state of knowledge on drivers and barriers to SDG 12.3 through a comprehensive literature review.

Design/methodology/approach

The authors employed a multi-step systematic literature review process and retrieved 171 studies addressing SDGs, with 83 explicitly addressing SDG 12.3. The analysis involved a qualitative content analysis of studies retrieved by analyzing key findings and relationships between drivers and barriers to FLW.

Findings

While academic research focuses on SDG 12.3 by stressing the necessity of FLW reduction, it fails to explain the drivers and barriers to minimizing FLW. The authors developed a conceptual framework to demonstrate how barriers and drivers can inhibit or stimulate the dynamics that will achieve SDG 12.3 through effective planning and management.

Research limitations/implications

This study addressed the theoretical limitations of existing studies and clarified the critical gaps in the current literature, thereby guiding future researchers in the food supply chain (FSC) context.

Originality/value

The research to date focused on high-income countries, and future empirical studies should focus on consumption patterns, the associated drivers and barriers of food waste in low-income countries and its social impact.
Understanding quondam commitments to retain employees: insights from the case of flight attendants and pilots
Authors: Peyrat-Guillard Dominique , Grefe Gwenaëlle , Subramanian Jeayaram
Published: September 2022

Purpose

This study aims to examine the process model of quondam commitments (commitments employees used to have, but no longer have). It is part of a new perspective aimed at understanding better the concept of commitment, a powerful determinant of employee retention, by looking at gone commitments.

Design/methodology/approach

Drawing on a qualitative methodology recommended in the most recent commitment literature, life story interviews (Study 1 – flight attendants) and non-directive interviews (Study 2 – pilots) were conducted.

Findings

The authors propose a revised process model of quondam commitments, including the possible transformation of a commitment bond into a different type of psychological bond over time.

Research limitations/implications

The sample sizes are limited because of the qualitative nature of both studies, and the quondam commitment outcomes could only be studied at the individual level. However, the innovative nature of the work offers important contributions and avenues for research.

Practical implications

This study provides concrete perspectives for hospitality professionals to retain employees who question their relationship with work. Its relevance goes beyond the airline sector and can be applied to the hotel or restaurant industry, looking for solutions to deal with massive attrition.

Originality/value

This research contributes to filling three gaps identified in the commitment literature. It is one of the very rare studies considering closely both multiple targets and multiple types of psychological bonds. Moreover, it incorporates their dynamics, beyond the commitment bond, and suggests a refined model.
How and when does internal and external social media use for marketing impact B2B SME performance?
Authors: Corral de Zubielqui Graciela , Jones Janice
Published: September 2022

Purpose

Despite its potential as a new source of competitive advantage, the performance implications of social media (SM) marketing (SMM) are not well understood. This study aims to investigate how and when SMM matters to firm performance, analysing the mediating role of product innovation (PI) and moderating the role of marketing innovation (MI) in business to business (B2B) small- and medium-sized enterprises (SMEs).

Design/methodology/approach

This paper used structural equation modelling analysis in STATA, using the Australian bureau of statistics data set of 4,956 SMEs which operate in the B2B environment.

Findings

The results reveal differential moderating effects of MI on the direct SMM–performance relationship. MI positively moderates internal SMM and SM use for promotion and branding on firm performance. MI also negatively moderates SM use for customer communication on firm performance, underscoring SMM constituting a double-edged sword. The indirect effects of internal SM use and SM use for promotion and branding, and customer involvement in new product development on performance via PI are significant when MI is absent.

Practical implications

Hence, B2B SMEs benefit from PI and existing SMM but do not benefit from dual PI and new MI.

Originality/value

By disaggregating SMM and explicating the mediating mechanism and moderating effects of MI, this study reveals how and under what conditions SMM matters to firm performance in B2B SMEs.