bluuebunny/crossref_metadata_2025_split huggingface dataset:
Does WASH FIT improve water, sanitation, and hygiene and related health impacts in healthcare facilities? A systematic review
Authors: Lineberger Hannah , Cronk Ryan , Kpodzro Sena , Salzberg Aaron , Anderson Darcy M. 
Published: April 2024

AbstractIntroductionEnvironmental health services (e.g., water, sanitation, hygiene, cleaning, waste management) in healthcare facilities are important to improve health outcomes and strengthen health systems, but coverage gaps remain. The World Health Organization and United Nations Children’s Fund developed WASH FIT, a quality improvement tool, to help assess and improve environmental health services. Fifty-three countries have adopted it. However, there is little evidence of its effectiveness. This systematic review evaluates whether WASH FIT improves environmental health services or associated health outcomes and impacts.MethodsWe conducted database searches to identify relevant studies and extracted data on study design, healthcare facility characteristics, and inputs, activities, outputs, outcomes, and impacts associated with WASH FIT. We summarized the findings using a logic model framework and narrative synthesis.ResultsWe included 31 studies in the review. Most inputs and activities were described qualitatively. Twenty-three studies reported quantitative outputs, primary WASH FIT indicator scores, and personnel trained on WASH FIT. Nine studies reported longitudinal data demonstrating changes in these outputs throughout WASH FIT implementation. Six studies reported quantitative outcomes measurements; the remainder described outcomes qualitatively or not at all. Common outcomes included allocated funding for environmental health services, community engagement, and government collaboration, changes in knowledge, attitudes, or practices among healthcare staff, patients, or community members, and policy changes. No studies directly measured impacts or evaluated WASH FIT against a rigorous control group.ConclusionsAvailable evidence is insufficient to evaluate WASH FIT’s effects on outputs, outcomes, and impacts. Further effort is needed to comprehensively identify the inputs and activities required to implement WASH FIT and to draw specific links between changes in outputs, outcomes, and impacts. Short-term opportunities exist to improve evidence by more comprehensive reporting of WASH FIT assessments and exploiting data on health impacts within health management information systems. In the long term, we recommend experimental studies. This evidence is important to ensure that funding invested for WASH FIT implementation is used cost-effectively and that opportunities to adapt and refine WASH FIT are fully realized as it continues to grow in use and influence.HighlightsWASH FIT is highly influential, but little is known about its effectivenessWe reviewed WASH FIT’s effects on environmental health service outputs and health impactsNine studies measured outputs longitudinally; none directly measured health impactsNo studies compared WASH FIT’s performance against a rigorous control groupEvidence is insufficient to assess WASH FIT’s effects on outputs or health impactsGraphical abstract
Mutant phenotypes and comprehensive expression analyses reveal roles for CLAVATA in moss vegetative and reproductive development and fertility
Authors: Venza Zoe Nemec , Greiff George R. L. , Harrison C. Jill 
Published: April 2024

AbstractThe CLAVATA pathway regulates meristem size in angiosperms, but bryophytes have distinct meristematic activities to vascular plants, and gametophytic CLAVATA functions are divergent between species. Here we analysed the promoter activities of all CLAVATA peptide and receptor-encoding genes in the mossPhyscomitrium patens, and using mutants, identified requirements for PpCLV1 and PpRPK2 receptors in male and female reproductive development and fertility. In gametophytes, all 12CLAVATAgenes were expressed in foraging filaments (caulonemata) and leaves (phyllids), but most tissues showed highly specific patterns of promoter activity.PpCLE3expression specifically marked gametophyte shoot (gametophore) apical cells andPpCLV1bandPpRPK2expression marked overlapping apical domains. Expression in male (antheridia) and female (archegonia and eggs) reproductive tissues led us to use mutants to identify roles forPpCLV1a, PpCLV1bandPpRPK2in fertility and reproductive development. In sporophytes, the foot was a common site ofPpCLEexpression, and all genes were expressed in stomata. NoPpCLEactivity specifically marked the embryonic apical cells, and embryonicPpCLV1bandPpRPK2expression marked distinct apical and basal domains. Thus,P. patensstem cell activity is likely regulated by different genes in gametophytes and sporophytes, and promoter evolution was a likely driver of diversification of CLAVATA function.Plain language summaryWhilst gene gain and duplication contributed to the origin of land plants and diversification of seed plants, significant gene loss is associated with morphological adaptation in bryophytes. In the moss,Physcomitrium patens,CLAVATAgenes expanded from low ancestral numbers, showing exquisite cell type specificity in expression. Our results suggest co-option of CLAVATA into many different developmental processes during moss evolution.
AlbuMAX supplemented media induces the formation of transmission-competentP. falciparumgametocytes
Authors: Graumans Wouter , van der Starre Alex , Stoter Rianne , van Gemert Geert-Jan , Andolina Chiara , Ramjith Jordache , Kooij Taco , Bousema Teun , Proellochs Nicholas 
Published: April 2024

AbstractAsexual blood stage culture ofPlasmodium falciparumis routinely performed but reproducibly inducing commitment to and maturation of viable gametocytes remains difficult. Culture media can be supplemented with human serum substitutes to induce commitment but these generally only allow for long-term culture of asexual parasites and not transmission-competent gametocytes due to their different lipid composition. Recent insights demonstrated the important roles lipids play in sexual commitment; elaborating on this we exposed ring stage parasites (20-24 hours hpi) for one day to AlbuMAX supplemented media to trigger induction to gametocytogenesis. We observed a significant increase in gametocytes after AlbuMAX induction compared to serum. We also tested the transmission potential of AlbuMAX inducted gametocytes and found a significant higher oocyst intensity compared to serum. We conclude that AlbuMAX supplemented media induces commitment, allows a more stable and predictable production of transmittable gametocytes than serum alone.HighlightsGametocytes are formed when asexual parasites commit to sexual differentiation.Sexual commitment can be promoted by environmental stressors in media formulations.Short exposure of young asexual parasites to the serum substitute AlbuMAX achieves high proportion of committed gametocytes that are transmission-competent.
Global organization of phenylpropanoid and anthocyanin pathways revealed by proximity labeling of trans-cinnamic acid 4-hydroxylase (CYP73A412) inPetunia inflatapetal protoplasts
Authors: Aravena-Calvo Javiera , Busck-Mellor Silas , Laursen Tomas 
Published: April 2024

ABSTRACTThe phenylpropanoid pathway is one of the main carbon sinks in plants, channeling phenylalanine towards thousands of products including monolignols, stilbenes, flavonoids and volatile compounds. The enzymatic steps involved in many of these pathways are well characterized, however the physical organization of these enzymes within the plant cell remains unknown Proximity-dependent labeling allows untargeted determination of protein interactionsin vivo, and therefore stands as an attractive alternative to targeted binary assays for determining global protein-protein interaction networks. In this study, we show a TurboID-based proximity labeling system developed to study protein interaction networks of the core phenylpropanoid pathway in petunia. Here, the endoplasmic reticulum (ER) membrane anchored cytochrome P450 cinnamic acid 4-hydroxylase (C4H, CYP73A412) fromPetunia inflatawas coupled to TurboID and expressed in protoplasts derived from anthocyanin-rich petunia petals. Potential interactors were isolated using streptavidin beads, digested and quantified by mass spectrometry. Among the enriched proteins, we identified multiple soluble enzymes from the late anthocyanin pathway, other CYP73 isoforms, as well as additional ER membrane anchored CYPs includingp-coumaric acid 3-hydroxylase (C3’H, CYP98A2). Our results suggest that CYP73A412 co-localizes with enzymes from the phenylpropanoid- and downstream anthocyanin pathways, supporting the idea that CYP73s may serve as ER anchoring points for these metabolic pathways. Moreover, this study demonstrates the feasibility of using protoplasts to perform global mapping of protein network for enzymes in their native cellular environment.
Merkel cell polyomavirus protein ALTO modulates TBK1 activity to support persistent infection
Authors: Wang Ranran , Senay Taylor E. , Luo Tiana T. , Regan James M. , Salisbury Nick , Galloway Denise , You Jianxin 
Published: April 2024

AbstractWhile Merkel cell polyomavirus (MCPyV or MCV) is an abundant virus frequently shed from healthy skin, it is one of the most lethal tumor viruses in immunocompromised individuals, highlighting the crucial role of host immunity in controlling MCPyV oncogenic potential. Despite its prevalence, very little is known about how MCPyV interfaces with the host immune response to maintain asymptomatic persistent infection and how inadequate control of MCPyV infection triggers MCC tumorigenesis. In this study, we discovered that the MCPyV protein, known as the Alternative Large Tumor Open Reading Frame (ALTO), effectively primes and activates the STING signaling pathway. It recruits Src kinase into the complex of STING downstream kinase TBK1 to trigger its autophosphorylation, which ultimately activates the subsequent antiviral immune response. Combining single-cell analysis with both loss- and gain-of-function studies of MCPyV infection, we demonstrated that the activity of ALTO leads to a decrease in MCPyV replication. Thus, we have identified ALTO as a crucial viral factor that modulates the STING-TBK1 pathway, creating a negative-feedback loop that limits viral infection and maintains a delicate balance with the host immune system. Our study reveals a novel mechanism by which a tumorigenic virus-encoded protein can link Src function in cell proliferation to the activation of innate immune signaling, thereby controlling viral spread and sustaining persistent infection. Our previous findings suggest that STING also functions as a tumor suppressor in MCPyV-driven oncogenesis. This research provides a foundation for investigating how disruptions in the finely tuned virus-host balance, maintained by STING, could alter the fate of MCPyV infection, potentially encouraging malignancy.Author summaryMerkel cell polyomavirus (MCPyV) is a small DNA virus responsible for the majority cases of Merkel Cell Carcinoma (MCC), a rare yet highly aggressive form of cancer. While MCPyV latently infects a vast majority of individuals, the mechanisms governing its control, persistence, and oncogenic triggers remain obscure. Our research reveals that the MCPyV-derived Alternative Large Tumor Open Reading Frame (ALTO) protein primes and activates the cGAS-STING- TBK1 innate immune pathway within cells. Such activation elicits an antiviral response, effectively curbing MCPyV replication. This phenomenon illustrates the virus’s cunning strategy to exploit cellular mechanisms, ensuring low viral presence while facilitating long-term infection. Consequently, our study sheds light on a novel tactic utilized by MCPyV to maintain a persistent infection in its host.
Fragility of ER homeostatic regulation underlies haploid instability in human somatic cells
Authors: Ishida-Ishihara Sumire , Yaguchi Kan , Sato Kimino , Yoshizawa Koya , Miura Sena , Yang Guang , Veszelyi Krisztina , Banhegyi Gabor , Margittai Eva , Uehara Ryota 
Published: April 2024

AbstractMammalian somatic cells are generally unstable in the haploid state, resulting in haploid-to-diploid conversion within a short time frame. However, cellular and molecular principles that limit the sustainability of somatic haploidy remain unknown. In this study, we found the haploidy-linked vulnerability to ER stress as a critical cause of haploid intolerance in human somatic cells. Pharmacological induction of ER stress selectively induced apoptosis in haploid cells, facilitating the replacement of haploids by co-existing diploidized cells in a caspase-dependent manner. Biochemical analyses revealed that unfolded protein response (UPR) was activated with similar dynamics between haploids and diploids upon ER stress induction. However, haploids were less efficient in solving proteotoxic status, resulting in a bias toward a proapoptotic mode of UPR signaling. Artificial replenishment of chaperone function or inhibition of a UPR signal transducer ATF6 substantially alleviated the haploidy-linked upregulation of proapoptotic signaling and improved haploid cell retention under ER stress. These data demonstrate that the ER stress-driven haploid instability stems from inefficient proteostatic control that alters the functionality of UPR to cause apoptosis selectively in haploids. Interestingly, haploids suffered a higher level of protein aggregation even in unperturbed conditions, and the long-term stability of the haploid state was significantly improved by alleviating their natural proteotoxicity. Based on these results, we propose that the haploidy-specific vulnerability to ER stress creates a fundamental cause of haploid intolerance in mammalian somatic cells. Our findings provide new insight into the principle that places a stringent restriction on the evolution of animal life cycles.
In vitrohost transcriptomics duringCryptococcus neoformans,Cryptococcus gattii, andCandida albicansinfection of South African volunteers
Authors: Doyle Ronan , Kannambath Shichina , Pittman Alan , Goliath Rene , Kumar Vinod , Meintjes Graeme , Milburn James , Netea Mihai G. , Harrison Thomas S , Jarvis Joseph N , Bicanic Tihana 
Published: April 2024

AbstractCryptococcus neoformans,Cryptococcus gattiiandCandida albicansare opportunistic fungal pathogens associated with infections in immunocompromised hosts. Cryptococcal meningitis (CM) is the leading fungal cause of HIV-related deaths globally, with the majority occurring in Africa. The human immune response toC. albicansinfection has been studied extensively in large genomics studies whereas cryptococcal infections, despite their severity, are comparatively understudied. Here we investigated the transcriptional response of immune cells afterin vitrostimulation within vitro C. neoformans,C. gattiiandC. albicansinfection of peripheral blood mononuclear cells (PBMCs) collected from healthy South African volunteers. We found a lower transcriptional response to cryptococcal stimuli compared toC. albicansand unique expression signatures from all three fungal stimuli. This work provides a starting point for further studies comparing the transcriptional signature of CM in immunocompromised patients, with the goal of identifying biomarkers of disease severity and possible novel treatment targets.
Cross Potential Selection: A Proposal for Optimizing Crossing Combinations in Recurrent Selection Based on the Ability of Future Inbred Lines
Authors: Sakurai Kengo , Hamazaki Kosuke , Inamori Minoru , Kaga Akito , Iwata Hiroyoshi 
Published: April 2024

ABSTRACTIn plant breeding programs, rapid production of novel varieties is highly desirable. Genomic selection allows the selection of superior individuals based on genomic estimated breeding values. However, it is worth noting that superior individuals may not always be superior parents. The choice of the crossing pair significantly influences the genotypic value of the resulting progeny. This study introduced a new strategy for selecting crossing pairs, termed Cross Potential Selection (CPS), designed to expedite the production of novel varieties. The CPS assesses the potential of each crossing pair to generate a novel variety. It considers the segregation of each crossing pair and computes the expected genotypic values of the topperforming individuals, assuming that the progeny distribution of genotypic values follows a normal distribution. We simulated a 10-year breeding program to compare CPS with three other selection strategies. CPS consistently demonstrated the highest genetic improvements among the four strategies in early cycles. In particular, during the middle cycles of the breeding program, CPS exhibited the highest genetic improvement of 73% of the 300 independent breeding simulations. In a long-term breeding scheme, some progeny distributions of genotypic values may deviate from normal distribution, affecting the efficiency of CPS. Nevertheless, compared with the other three strategies, CPS achieved significant short-term genetic improvements. In conclusion, CPS holds substantial promise for enhancing the efficiency of plant breeding programs.Article SummaryThis study introduces a novel plant breeding strategy termed Cross Potential Selection (CPS), which was designed to expedite the production of novel varieties. The CPS evaluates the potential of each crossing pair for the target generation. Through comparative breeding simulations, CPS demonstrated superior performance over the three alternative breeding strategies, particularly in the early cycles. These findings suggest that CPS holds significant promise for enhancing plant breeding efficiency.
Construction of whole cell bacterial biosensors as an alternative environmental monitoring technology to detect naphthenic acids in oil sands process-affected water
Authors: Bookout Tyson , Shideler Steve , Cooper Evan , Goff Kira , Headley John V , Gieg Lisa M , Lewenza Shawn 
Published: April 2024

AbstractAfter extraction of bitumen from oil sands deposits, the oil sand process-affected water (OSPW) is stored in tailings ponds. Naphthenic acids in tailings ponds have been identified as the primary contributor to toxicity to aquatic life. As an alternative to other analytical methods, here we identify bacterial genes induced after growth in naphthenic acids and use synthetic biology approaches to construct a panel of candidate biosensors for NA detection in water. The main promoters of interest were theatuARpromoters from a naphthenic acid degradation operon and upstream TetR regulator, themarRoperon which includes a MarR regulator and downstream naphthenic acid resistance genes, and a hypothetical gene with a possible role in fatty acid biology. Promoters were printed and cloned as transcriptionalluxreporter plasmids that were introduced into a tailings pond-derivedPseudomonasspecies. All candidate biosensor strains were tested for transcriptional responses to naphthenic acid mixtures and individual compounds. The three priority promoters respond in a dose-dependent manner, which allows semi-quantitative measurements, to simple, acyclic and complex NA mixtures, and each promoter has unique NA specificities. The limits of NA detection from the various NA mixtures ranged between 1.5 - 15 mg/L. TheatuAandmarRpromoters also detected NA in small volumes of OSPW samples and were induced by extracts of the panel of OSPW samples. While biosensors have been constructed for other hydrocarbons, here we describe a biosensor approach that could be employed in environmental monitoring of naphthenic acids in oil sands mining wastewater.
Identification of transposable element families from pangenome polymorphisms
Authors: Sierra Pío , Durbin Richard 
Published: April 2024

AbstractBackgroundTransposable Elements (TEs) are fragments of DNA, typically a few hundred base pairs up to several tens of thousands bases long, that have the ability to generate new copies of themselves in the genome. Most existing methods used to identify TEs in a newly sequenced genome are based on their repetitive character, together with detection based on homology and structural features. As new high quality assemblies become more common, including the availability of multiple independent assemblies from the same species, an alternative strategy for identification of TE families becomes possible in which we focus on the polymorphism at insertion sites caused by TE mobility.ResultsWe develop the idea of using the structural polymorphisms found in pangenomes to create a library of the TE families recently active in a species, or in a closely related group of species. We present a tool,pantera, that achieves this task, and illustrate its use both on species with well-curated libraries, and on new assemblies.ConclusionsOur results show thatpanterais sensitive and accurate, tending to correctly identify complete elements with precise boundaries, and is particularly well suited to detect larger, low copy number TEs that are often undetected with existing de novo methods.
AVibrio choleraeType IV restriction system targets glucosylated 5-hydroxyl methyl cytosine to protect against phage infection
Authors: Gomez Jasper B. , Waters Christopher M. 
Published: April 2024

AbstractA major challenge faced byVibrio choleraeis constant predation by bacteriophage (phage) in aquatic reservoirs and during infection of human hosts. To overcome phage predation,V. choleraehas evolved a myriad of phage defense systems. Although several novel defense systems have been discovered, we hypothesized more were encoded inV. choleraegiven the relative paucity of phage that have been isolated which infect this species. Using aV. choleraegenomic library, we identified a Type IV restriction system consisting of two genes within a 16kB region of theVibriopathogenicity island-2 that we name TgvA and TgvB (Type I-embeddedgmrSD-like system ofVPI-2). We show that both TgvA and TgvB are required for defense against T2, T4, and T6 by targeting glucosylated 5-hydroxymethylcytosine (5hmC). T2 or T4 phages that lose the glucose modification are resistant to TgvAB defense but exhibit a significant evolutionary tradeoff becoming susceptible to other Type IV restriction systems that target unglucosylated 5hmC. We show that additional phage defense genes are encoded in VPI-2 that protect against other phage like T3, secΦ18, secΦ27 and λ. Our study uncovers a novel Type IV restriction system inV. cholerae, increasing our understanding of the evolution and ecology ofV. choleraewhile highlighting the evolutionary interplay between restriction systems and phage genome modification.Abstract ImportanceBacteria are constantly being predated by bacteriophage (phage). To counteract this predation, bacteria have evolved a myriad of defense systems. Some of these systems specifically digest infecting phage by recognizing unique base modifications present on the phage DNA. Here, we discover a Type IV restriction system encoded inV. choleraethat we name TgvAB and demonstrate it recognizes and restricts phage that have 5-hydroxymethylcytosine glucosylated DNA. Moreover, the evolution of resistance to TgvAB render phage susceptible to other Type IV restriction systems, demonstrating a significant evolutionary tradeoff. These results enhance our understanding of the evolution ofV. choleraeand more broadly how bacteria evade phage predation.