Salinity impacts on humidification dehumidification (HDH) desalination systems: review.

The use of humidification-dehumidification water desalination technology has been shown to be a practical means of meeting the demand for freshwater. The aim of this review is to investigate the impact of salinity on HDH techniques that have various benefits in terms of both economics and the environment, including the capacity to operate at low temperatures, utilize sustainable energy sources, the need for low maintenance, and straightforward construction requirements. Also, in this review, it is observed that the HDH system's components are strong and capable of treating severely salinized water. It can treat water in an appropriate way than other desalination technologies. This technology has recently been commercialized to treat highly salinized generated water. However, more research is needed to determine how salinity affects HDH productivity. According to several research investigations, while the specific thermal energy consumption increased considerably and the productivity of water per unit of time decreased significantly as the salt mass percentage grew, the purity of clean water did not suffer. The rejected brine must be reduced by increasing the total water recovery ratio in the HDH system. Through this review, it was found that brine control is becoming increasingly important in the water processing industry. ZLD systems, which aim to recover both freshwater and solid salts, can be a viable replacement for disposal methods. Finally, through this reviewer, it was concluded that HDH desalination systems may operate with extremely saline water while increasing salinity has a significant influence on system performance.

Selenium supplementation in thyroid eye disease: an updated review from a clinical ophthalmic perspective.

Thyroid eye disease (TED) consists of a spectrum of autoimmune orbital pathology that threatens patients' quality of life and vision. Research suggests that oxidative stress plays a role in both the thyroid gland and orbit. Selenium has been proposed as a potential therapeutic adjunct given its role in thyroid physiology and antioxidant metabolism. Furthermore, selenium status has been linked to multiple pathological thyroid states. Despite the preponderance of evidence demonstrating a role for selenium in thyroid disease, limited research exists highlighting its role in TED specifically. This review summarizes the pathophysiology and role of selenium in thyroid eye disease (TED) and the current body of evidence including in vitro and in vivo studies highlighting the role for supplementation in clinical ophthalmic practice. Notably, relatively lower selenium levels have been shown to have a modest correlation with severity of thyroid eye disease. Selenium supplementation has shown some benefit in patients with mild Graves' Orbitopathy in European populations presumed deficient. Despite the preponderance of evidence demonstrating a role for selenium in thyroid disease, limited data is available to conclusively expand its role in TED outside of a 6-month course of supplementation in selenium deficient or relatively deficient populations. Data subject to geographic and population differences in selenium levels limits the generalizability of supplementation in TED. Despite mechanistic evidence of its antioxidant effects in TED beyond the advantages of thyroid disease in general, the benefits of selenium supplementation should be interrogated further and contextually tailored in both clinical and research formats for ophthalmic practice.

Exergoeconomic and enviroeconomic evaluations of conventional solar still using PCM and electric heater powered by solar energy: an experimental study.

Solar stills are used in distant and arid areas to convert brackish or salty water into potable water fit for human use in a simple, affordable, and effective manner. Even when PCM materials are used, typical solar systems still have minimal production per day. In this study, experimental tests were carried out in order to increase the performance of a single-slope solar still combined with PCM material (paraffin wax) and a solar-powered electric heater. Two identical single-slope solar stills were designed, fabricated, and tested under the same climatic conditions during the summer and spring seasons of 2021 in Al-Arish, Egypt. The first is a conventional solar still (CVSS), and the other is also a conventional still but with PCM and an electric heater (CVSSWPCM). Several parameters were measured during the experiments, including sun intensity, meteorological aspects, cumulative freshwater production, average glass, and water temperatures and PCM temperature. The improved solar still was evaluated at different operating temperatures and was compared to the conventional traditional one. There were four cases studied: one case without a heater (paraffin wax only) and three other cases with a heater operating at 58 °C, 60 °C, and 65 °C, respectively. The experimental results revealed that activating the heater inside the paraffin wax increased daily production (i) in the spring by 2.38, 2.66, and 3.1 times and (ii) and in the summer by 2.2, 2.39, and 2.67 times at the three above-mentioned temperatures respectively (when compared to the traditional still). In addition, the maximum rate of daily freshwater production was achieved at paraffin wax temperature of 65 °C in both spring and summer (Case 5). Finally, the economic evaluation of the modified solar still was carried out according to cost per litre. The modified solar still with a heater operating at 65 °C has a higher exergoeconomic value than the traditional one. The maximum CO2 mitigation in cases 1 and 5 was approximately 28 tons and 160 tons, respectively.

Functional signatures of ex-vivo dental caries onset.

Background: The etiology of dental caries remains poorly understood. With the advent of next-generation sequencing, a number of studies have focused on the microbial ecology of the disease. However, taxonomic associations with caries have not been consistent. Researchers have also pursued function-centric studies of the caries microbial communities aiming to identify consistently conserved functional pathways. A major question is whether changes in microbiome are a cause or a consequence of the disease. Thus, there is a critical need to define conserved functional signatures at the onset of dental caries. Methods: Since it is unethical to induce carious lesions clinically, we developed an innovative longitudinal ex-vivo model integrated with the advanced non-invasive multiphoton second harmonic generation bioimaging to spot the very early signs of dental caries, combined with 16S rRNA short amplicon sequencing and liquid chromatography-mass spectrometry-based targeted metabolomics. Findings: For the first time, we induced longitudinally monitored caries lesions validated with the scanning electron microscope. Consequently, we spotted the caries onset and, associated with it, distinguished five differentiating metabolites - Lactate, Pyruvate, Dihydroxyacetone phosphate, Glyceraldehyde 3-phosphate (upregulated) and Fumarate (downregulated). Those metabolites co-occurred with certain bacterial taxa; Streptococcus, Veillonella, Actinomyces, Porphyromonas, Fusobacterium, and Granulicatella, regardless of the abundance of other taxa. Interpretation: These findings are crucial for understanding the etiology and dynamics of dental caries, and devising targeted interventions to prevent disease progression.

Current State and Challenges of the Global Outcomes of Dental Caries Research in the Meta-Omics Era.

Despite significant healthcare advances in the 21st century, the exact etiology of dental caries remains unsolved. The past two decades have witnessed a tremendous growth in our understanding of dental caries amid the advent of revolutionary omics technologies. Accordingly, a consensus has been reached that dental caries is a community-scale metabolic disorder, and its etiology is beyond a single causative organism. This conclusion was based on a variety of microbiome studies following the flow of information along the central dogma of biology from genomic data to the end products of metabolism. These studies were facilitated by the unprecedented growth of the next- generation sequencing tools and omics techniques, such as metagenomics and metatranscriptomics, to estimate the community composition of oral microbiome and its functional potential. Furthermore, the rapidly evolving proteomics and metabolomics platforms, including nuclear magnetic resonance spectroscopy and/or mass spectrometry coupled with chromatography, have enabled precise quantification of the translational outcomes. Although the majority supports 'conserved functional changes' as indicators of dysbiosis, it remains unclear how caries dynamics impact the microbiota functions and vice versa, over the course of disease onset and progression. What compounds the situation is the host-microbiota crosstalk. Genome-wide association studies have been undertaken to elucidate the interaction of host genetic variation with the microbiome. However, these studies are challenged by the complex interaction of host genetics and environmental factors. All these complementary approaches need to be orchestrated to capture the key players in this multifactorial disease. Herein, we critically review the milestones in caries research focusing on the state-of-art singular and integrative omics studies, supplemented with a bibliographic network analysis to address the oral microbiome, the host factors, and their interactions. Additionally, we highlight gaps in the dental literature and shed light on critical future research questions and study designs that could unravel the complexities of dental caries, the most globally widespread disease.

FMRF-NH2 -related neuropeptides in Biomphalaria spp., intermediate hosts for schistosomiasis: Precursor organization and immunohistochemical localization.

Freshwater snails of the genus Biomphalaria serve as intermediate hosts for the digenetic trematode Schistosoma mansoni, the etiological agent for the most widespread form of intestinal schistosomiasis. As neuropeptide signaling in host snails can be altered by trematode infection, a neural transcriptomics approach was undertaken to identify peptide precursors in Biomphalaria glabrata, the major intermediate host for S. mansoni in the Western Hemisphere. Three transcripts that encode peptides belonging to the FMRF-NH2 -related peptide (FaRP) family were identified in B. glabrata. One transcript encoded a precursor polypeptide (Bgl-FaRP1; 292 amino acids) that included eight copies of the tetrapeptide FMRF-NH2 and single copies of FIRF-NH2 , FLRF-NH2 , and pQFYRI-NH2 . The second transcript encoded a precursor (Bgl-FaRP2; 347 amino acids) that comprised 14 copies of the heptapeptide GDPFLRF-NH2 and 1 copy of SKPYMRF-NH2 . The precursor encoded by the third transcript (Bgl-FaRP3; 287 amino acids) recapitulated Bgl-FaRP2 but lacked the full SKPYMRF-NH2 peptide. The three precursors shared a common signal peptide, suggesting a genomic organization described previously in gastropods. Immunohistochemical studies were performed on the nervous systems of B. glabrata and B. alexandrina, a major intermediate host for S. mansoni in Egypt. FMRF-NH2 -like immunoreactive (FMRF-NH2 -li) neurons were located in regions of the central nervous system associated with reproduction, feeding, and cardiorespiration. Antisera raised against non-FMRF-NH2 peptides present in the tetrapeptide and heptapeptide precursors labeled independent subsets of the FMRF-NH2 -li neurons. This study supports the participation of FMRF-NH2 -related neuropeptides in the regulation of vital physiological and behavioral systems that are altered by parasitism in Biomphalaria.

MQF and buffered MQF: quotient filters for efficient storage of k-mers with their counts and metadata.

BACKGROUND: Specialized data structures are required for online algorithms to efficiently handle large sequencing datasets. The counting quotient filter (CQF), a compact hashtable, can efficiently store k-mers with a skewed distribution. RESULT: Here, we present the mixed-counters quotient filter (MQF) as a new variant of the CQF with novel counting and labeling systems. The new counting system adapts to a wider range of data distributions for increased space efficiency and is faster than the CQF for insertions and queries in most of the tested scenarios. A buffered version of the MQF can offload storage to disk, trading speed of insertions and queries for a significant memory reduction. The labeling system provides a flexible framework for assigning labels to member items while maintaining good data locality and a concise memory representation. These labels serve as a minimal perfect hash function but are ~ tenfold faster than BBhash, with no need to re-analyze the original data for further insertions or deletions. CONCLUSIONS: The MQF is a flexible and efficient data structure that extends our ability to work with high throughput sequencing data.

One-step generation of a targeted knock-in calf using the CRISPR-Cas9 system in bovine zygotes.

BACKGROUND: The homologous recombination (HR) pathway is largely inactive in early embryos prior to the first cell division, making it difficult to achieve targeted gene knock-ins. The homology-mediated end joining (HMEJ)-based strategy has been shown to increase knock-in efficiency relative to HR, non-homologous end joining (NHEJ), and microhomology-mediated end joining (MMEJ) strategies in non-dividing cells. RESULTS: By introducing gRNA/Cas9 ribonucleoprotein complex and a HMEJ-based donor template with 1 kb homology arms flanked by the H11 safe harbor locus gRNA target site, knock-in rates of 40% of a 5.1 kb bovine sex-determining region Y (SRY)-green fluorescent protein (GFP) template were achieved in Bos taurus zygotes. Embryos that developed to the blastocyst stage were screened for GFP, and nine were transferred to recipient cows resulting in a live phenotypically normal bull calf. Genomic analyses revealed no wildtype sequence at the H11 target site, but rather a 26 bp insertion allele, and a complex 38 kb knock-in allele with seven copies of the SRY-GFP template and a single copy of the donor plasmid backbone. An additional minor 18 kb allele was detected that looks to be a derivative of the 38 kb allele resulting from the deletion of an inverted repeat of four copies of the SRY-GFP template. CONCLUSION: The allelic heterogeneity in this biallelic knock-in calf appears to have resulted from a combination of homology directed repair, homology independent targeted insertion by blunt-end ligation, NHEJ, and rearrangement following editing of the gRNA target site in the donor template. This study illustrates the potential to produce targeted gene knock-in animals by direct cytoplasmic injection of bovine embryos with gRNA/Cas9, although further optimization is required to ensure a precise single-copy gene integration event.

A Missense Variant in ALDH5A1 Associated with Canine Succinic Semialdehyde Dehydrogenase Deficiency (SSADHD) in the Saluki Dog.

Dogs provide highly valuable models of human disease due to the similarity in phenotype presentation and the ease of genetic analysis. Seven Saluki puppies were investigated for neurological abnormalities including seizures and altered behavior. Magnetic resonance imaging showed a diffuse, marked reduction in cerebral cortical thickness, and symmetrical T2 hyperintensity in specific brain regions. Cerebral cortical atrophy with vacuolation (status spongiosus) was noted on necropsy. Genome-wide association study of 7 affected and 28 normal Salukis revealed a genome-wide significantly associated region on CFA 35. Whole-genome sequencing of three confirmed cases from three different litters revealed a homozygous missense variant within the aldehyde dehydrogenase 5 family member A1 (ALDH5A1) gene (XM_014110599.2: c.866G>A; XP_013966074.2: p.(Gly288Asp). ALDH5A1 encodes a succinic semialdehyde dehydrogenase (SSADH) enzyme critical in the gamma-aminobutyric acid neurotransmitter (GABA) metabolic pathway. Metabolic screening of affected dogs showed markedly elevated gamma-hydroxybutyric acid in serum, cerebrospinal fluid (CSF) and brain, and elevated succinate semialdehyde in urine, CSF and brain. SSADH activity in the brain of affected dogs was low. Affected Saluki dogs had striking similarities to SSADH deficiency in humans although hydroxybutyric aciduria was absent in affected dogs. ALDH5A1-related SSADH deficiency in Salukis provides a unique translational large animal model for the development of novel therapeutic strategies.

Comparison of Poly-A+ Selection and rRNA Depletion in Detection of lncRNA in Two Equine Tissues Using RNA-seq.

Long non-coding RNAs (lncRNAs) are untranslated regulatory transcripts longer than 200 nucleotides that can play a role in transcriptional, post-translational, and epigenetic regulation. Traditionally, RNA-sequencing (RNA-seq) libraries have been created by isolating transcriptomic RNA via poly-A+ selection. In the past 10 years, methods to perform ribosomal RNA (rRNA) depletion of total RNA have been developed as an alternative, aiming for better coverage of whole transcriptomic RNA, both polyadenylated and non-polyadenylated transcripts. The purpose of this study was to determine which library preparation method is optimal for lncRNA investigations in the horse. Using liver and cerebral parietal lobe tissues from two healthy Thoroughbred mares, RNA-seq libraries were prepared using standard poly-A+ selection and rRNA-depletion methods. Averaging the two biologic replicates, poly-A+ selection yielded 327 and 773 more unique lncRNA transcripts for liver and parietal lobe, respectively. More lncRNA were found to be unique to poly-A+ selected libraries, and rRNA-depletion identified small nucleolar RNA (snoRNA) to have a higher relative expression than in the poly-A+ selected libraries. Overall, poly-A+ selection provides a more thorough identification of total lncRNA in equine tissues while rRNA-depletion may allow for easier detection of snoRNAs.

Whole genome sequencing for mutation discovery in a single case of lysosomal storage disease (MPS type 1) in the dog.

Mucopolysaccharidosis (MPS) is a metabolic storage disorder caused by the deficiency of any lysosomal enzyme required for the breakdown of glycosaminoglycans. A 15-month-old Boston Terrier presented with clinical signs consistent with lysosomal storage disease including corneal opacities, multifocal central nervous system disease and progressively worsening clinical course. Diagnosis was confirmed at necropsy based on histopathologic evaluation of multiple organs demonstrating accumulation of mucopolysaccharides. Whole genome sequencing was used to uncover a frame-shift insertion affecting the alpha-L-iduronidase (IDUA) gene (c.19_20insCGGCCCCC), a mutation confirmed in another Boston Terrier presented 2 years later with a similar clinical picture. Both dogs were homozygous for the IDUA mutation and shared coat colors not recognized as normal for the breed by the American Kennel Club. In contrast, the mutation was not detected in 120 unrelated Boston Terriers as well as 202 dogs from other breeds. Recent inbreeding to select for recessive and unusual coat colors may have concentrated this relatively rare allele in the breed. The identification of the variant enables ante-mortem diagnosis of similar cases and selective breeding to avoid the spread of this disease in the breed. Boston Terriers carrying this variant represent a promising model for MPS I with neurological abnormalities in humans.

Author Correction: Genomic and phenotypic analyses of six offspring of a genome-edited hornless bull.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Genomic and phenotypic analyses of six offspring of a genome-edited hornless bull.

Genome editing followed by reproductive cloning was previously used to produce two hornless dairy bulls. We crossed one genome-edited dairy bull, homozygous for the dominant PC Celtic POLLED allele, with horned cows (pp) and obtained six heterozygous (PCp) polled calves. The calves had no horns and were otherwise healthy and phenotypically unremarkable. We conducted whole-genome sequencing of all animals using an Illumina HiSeq4000 to achieve ~20× coverage. Bioinformatics analyses revealed the bull was a compound heterozygote, carrying one naturally occurring PC Celtic POLLED allele and an allele containing an additional introgression of the homology-directed repair donor plasmid along with the PC Celtic allele. These alleles segregated in the offspring of this bull, and inheritance of either allele produced polled calves. No other unintended genomic alterations were observed. These data can be used to inform conversations in the scientific community, with regulatory authorities and with the public around 'intentional genomic alterations' and future regulatory actions regarding genome-edited animals.

Endogenous Avian Leukosis Virus in Combination with Serotype 2 Marek's Disease Virus Significantly Boosted the Incidence of Lymphoid Leukosis-Like Bursal Lymphomas in Susceptible Chickens.

In 2010, sporadic cases of avian leukosis virus (ALV)-like bursal lymphoma, also known as spontaneous lymphoid leukosis (LL)-like tumors, were identified in two commercial broiler breeder flocks in the absence of exogenous ALV infection. Two individual ALV subgroup E (ALV-E) field strains, designated AF227 and AF229, were isolated from two different breeder farms. The role of these ALV-E field isolates in development of and the potential joint impact in conjunction with a Marek's disease virus (MDV) vaccine (SB-1) were further characterized in chickens of an experimental line and commercial broiler breeders. The experimental line 0.TVB*S1, commonly known as the rapid feathering-susceptible (RFS) line, of chickens lacks all endogenous ALV and is fully susceptible to all subgroups of ALV, including ALV-E. Spontaneous LL-like tumors occurred following infection with AF227, AF229, and a reference ALV-E strain, RAV60, in RFS chickens. Vaccination with serotype 2 MDV, SB-1, in addition to AF227 or AF229 inoculation, significantly enhanced the spontaneous LL-like tumor incidence in the RFS chickens. The spontaneous LL-like tumor incidence jumped from 14% by AF227 alone to 42 to 43% by AF227 in combination with SB-1 in the RFS chickens under controlled conditions. RNA-sequencing analysis of the LL-like lymphomas and nonmalignant bursa tissues of the RFS line of birds identified hundreds of differentially expressed genes that are reportedly involved in key biological processes and pathways, including signaling and signal transduction pathways. The data from this study suggested that both ALV-E and MDV-2 play an important role in enhancement of the spontaneous LL-like tumors in susceptible chickens. The underlying mechanism may be complex and involved in many chicken genes and pathways, including signal transduction pathways and immune system processes, in addition to reported viral genes.IMPORTANCE Lymphoid leukosis (LL)-like lymphoma is a low-incidence yet costly and poorly understood disease of domestic chickens. The observed unique characteristics of LL-like lymphomas are that the incidence of the disease is chicken line dependent; pathologically, it appeared to mimic avian leukosis but is free of exogenous ALV infection; inoculation of the nonpathogenic ALV-E or MDV-2 (SB-1) boosts the incidence of the disease; and inoculation of both the nonpathogenic ALV-E and SB-1 escalates it to much higher levels. This study was designed to test the impact of two new ALV-E isolates, recently derived from commercial broiler breeder flocks, in combination with the nonpathogenic SB-1 on LL-like lymphoma incidences in both an experimental egg layer line of chickens and a commercial broiler breeder line of chickens under a controlled condition. Data from this study provided an additional piece of experimental evidence on the potency of nonpathogenic ALV-E, MDV-2, and ALV-E plus MDV-2 in boosting the incidence of LL-like lymphomas in susceptible chickens. This study also generated the first piece of genomic evidence that suggests host transcriptomic variation plays an important role in modulating LL-like lymphoma formation.

Acute mastoiditis: 20 years of experience with a uniform management protocol.

OBJECTIVES: To characterize the clinical presentation of pediatric patients who, upon AM diagnosis, also had imaging-diagnosed ICCs (ID-ICCs); to define the group of AM patients at risk of developing ID-ICCs; and to update knowledge about organisms causing AM. STUDY DESIGN: Analysis of all AM patients admitted between 1997 and 2018 and treated according to an obligatory protocol including both brain imaging and sampling for bacterial culture upon clinical diagnosis of AM. RESULTS: Of 166 admitted patients (0.5-19 years old) 22 (13%) already had ID-ICCs. In patients who, on admission, had already received antibiotics for acute otitis media (AOM) and also had CRP (C-reactive protein) levels above 93.5 mg/L, the risk of ID-CC was increased by 22.5-fold (P < 0.0001). Bacterial culture results were available for all patients and were positive in 115 (69%). Organisms most commonly found in patients without prior antibiotic treatment were group A Streptococcus pyogenes (53%), Streptococcus pneumoniae (23%), and Haemophylus influenzae (11%), while with prior antibiotic treatment they were Fusobacterium necrophorum (21%), Streptococcus pyogenes (18%) and Pseudomonas aeruginosa (18%). CONCLUSIONS: Since the risk of ID-ICC in patients with the abovementioned CRP and prior antibiotic treatment was significantly higher than in the others, these high-risk patients should undergo diagnostic imaging on admission. Antibiotic treatment prior to AM development may promote growth of non-AOM pathogen.

The TFAP2A-IRF6-GRHL3 genetic pathway is conserved in neurulation.

Mutations in IRF6, TFAP2A and GRHL3 cause orofacial clefting syndromes in humans. However, Tfap2a and Grhl3 are also required for neurulation in mice. Here, we found that homeostasis of Irf6 is also required for development of the neural tube and associated structures. Over-expression of Irf6 caused exencephaly, a rostral neural tube defect, through suppression of Tfap2a and Grhl3 expression. Conversely, loss of Irf6 function caused a curly tail and coincided with a reduction of Tfap2a and Grhl3 expression in tail tissues. To test whether Irf6 function in neurulation was conserved, we sequenced samples obtained from human cases of spina bifida and anencephaly. We found two likely disease-causing variants in two samples from patients with spina bifida. Overall, these data suggest that the Tfap2a-Irf6-Grhl3 genetic pathway is shared by two embryologically distinct morphogenetic events that previously were considered independent during mammalian development. In addition, these data suggest new candidates to delineate the genetic architecture of neural tube defects and new therapeutic targets to prevent this common birth defect.

Whole genome variant association across 100 dogs identifies a frame shift mutation in DISHEVELLED 2 which contributes to Robinow-like syndrome in Bulldogs and related screw tail dog breeds.

Domestic dog breeds exhibit remarkable morphological variations that result from centuries of artificial selection and breeding. Identifying the genetic changes that contribute to these variations could provide critical insights into the molecular basis of tissue and organismal morphogenesis. Bulldogs, French Bulldogs and Boston Terriers share many morphological and disease-predisposition traits, including brachycephalic skull morphology, widely set eyes and short stature. Unlike other brachycephalic dogs, these breeds also exhibit vertebral malformations that result in a truncated, kinked tail (screw tail). Whole genome sequencing of 100 dogs from 21 breeds identified 12.4 million bi-allelic variants that met inclusion criteria. Whole Genome Association of these variants with the breed defining phenotype of screw tail was performed using 10 cases and 84 controls and identified a frameshift mutation in the WNT pathway gene DISHEVELLED 2 (DVL2) (Chr5: 32195043_32195044del, p = 4.37 X 10-37) as the most strongly associated variant in the canine genome. This DVL2 variant was fixed in Bulldogs and French Bulldogs and had a high allele frequency (0.94) in Boston Terriers. The DVL2 variant segregated with thoracic and caudal vertebral column malformations in a recessive manner with incomplete and variable penetrance for thoracic vertebral malformations between different breeds. Importantly, analogous frameshift mutations in the human DVL1 and DVL3 genes cause Robinow syndrome, a congenital disorder characterized by similar craniofacial, limb and vertebral malformations. Analysis of the canine DVL2 variant protein showed that its ability to undergo WNT-induced phosphorylation is reduced, suggesting that altered WNT signaling may contribute to the Robinow-like syndrome in the screwtail breeds.