The transport of mannitol in Sinorhizobium meliloti is carried out by a broad-substrate polyol transporter SmoEFGK and is affected by the ability to transport and metabolize fructose.

The smo locus (sorbitol mannitol oxidation) is found on the chromosome of S. meliloti's tripartite genome. Mutations at the smo locus reduce or abolish the ability of the bacterium to grow on several carbon sources, including sorbitol, mannitol, galactitol, d-arabitol and maltitol. The contribution of the smo locus to the metabolism of these compounds has not been previously investigated. Genetic complementation of mutant strains revealed that smoS is responsible for growth on sorbitol and galactitol, while mtlK restores growth on mannitol and d-arabitol. Dehydrogenase assays demonstrate that SmoS and MtlK are NAD+-dependent dehydrogenases catalysing the oxidation of their specific substrates. Transport experiments using a radiolabeled substrate indicate that sorbitol, mannitol and d-arabitol are primarily transported into the cell by the ABC transporter encoded by smoEFGK. Additionally, it was found that a mutation in either frcK, which is found in an operon that encodes the fructose ABC transporter, or a mutation in frk, which encodes fructose kinase, leads to the induction of mannitol transport.

ß-Galactosidase therapy can mitigate blood galactose elevation after an oral lactose load in galactose mutarotase deficiency.

Galactose mutarotase (GALM) deficiency (MIM# 618881), also known as type IV galactosemia, is caused by biallelic pathogenic variants of GALM. Cataracts are observed in patients with GALM deficiency as well as in other conditions associated with high levels of blood galactose and can be prevented by consuming a galactose-restricted diet or formula. Galactose restriction is the only known treatment for GALM deficiency and other types of galactosemia. We incidentally found that ß-galactosidase might reduce blood galactose levels caused by lactose loading in GALM deficiency. Consequently, we investigated the effectiveness of ß-galactosidase in decreasing the level of blood galactose in three patients with GALM deficiency. We performed two lactose loading tests per case: one with and one without ß-galactosidase. The add-on administration of ß-galactosidase significantly mitigated blood galactose elevations after lactose loading. Although urine galactitol was mildly elevated in all patients with GALM deficiency, ß-galactosidase did not prevent increased levels of urine galactitol during the loading tests. No adverse events, including cataracts, were observed during or after the tests. Therefore, ß-galactosidase could be a potential novel treatment agent for blood galactose elevation caused by lactose in patients with GALM deficiency. The effectiveness of ß-galactosidase could possibly result in loosening of the galactose dietary restrictions or treatment for patients with GALM deficiency.

Precyclization Conformer Profiles of -SiR3+- and -Bcat+-Activated Linear Si-Protected Hexitols Explain Condensative Cyclization Selectivities.

The condensative cyclization of sp3 C-O bonds in per-silylated hexitols is investigated by computation. Conformer searches using the Monte Carlo algorithm, followed by successively higher levels of theory (MMFF, PM3, and B3LYP), of -SiR3+- and -Bcat+-activated substrates lead to structures primed for intramolecular chemistry. Silane activation features O4 to C1 attack, while borane activation suggests boronium ions that activate O5 to C2 reactivity. This, in conjunction with Boltzmann population analysis, parallels reported reactivity for sorbitol, mannitol, and galactitol. Calculations using the meta-hybrid M06-2X functional additionally provide free-energy profiles for each cyclization event. In most of the cases presented, precyclization conformers that position a nucleophilic oxygen less than 3.0 Å from the C-O leaving group correlate to efficient experimental reactivities. Two examples of galactitol containing bridging silyl groups are analyzed computationally, and the experimental outcomes match predictions. The computational regime presented is a step closer to providing predictive power for the reduction of per-functionalized molecules.

Utility of CHROMagar™ Candida Plus for presumptive identification of Candida auris from surveillance samples.

Candida auris is a nosocomial fungal pathogen of prime importance due to its global emergence and rapid spread in healthcare facilities worldwide. One important concern is that routine, conventional methods fail to identify C. auris. While molecular and protein-based assays accurately detect/identify C. auris, these methods are time-consuming, expensive, and require expertise. Therefore, the objective of the present study was to assess the potential use of a novel chromogenic medium, CHROMagar™ Candida Plus, as an economical alternative to expensive and laborious diagnostic tests. We compared CHROMagar™ Candida Plus with the standard enrichment (salt Sabouraud Dulcitol broth) medium to test the recovery efficiency of C. auris from surveillance samples. We also tested CHROMagar™ Candida Plus for its ability to distinguish C. auris from other yeast species. One hundred surveillance samples were cultured on CHROMagar™ Candida Plus and Dulcitol broth and incubated at 37 °C and 40 °C, respectively. Additionally, 32 Candida and yeast species were cultured on CHROMagar™ Candida Plus at 37 °C for three days to rule out any close resemblance to C. auris. Of 100 surveillance samples tested, 69 yielded presumptive positive C. auris exhibiting creamy pink colonies with a blue halo on CHROMagar™ Candida Plus within three days of incubation, and MALDI-TOF MS confirmed all by day 4. On the other hand, 69 of 100 surveillance samples yielded turbidity in Dulcitol broth by days 3-14 with final MALDI identification by days 5 to 17. Both media failed to identify one sample each, resulting in assay sensitivity and specificity of 99% and 97%, respectively. Of Candida and yeast species tested, 75-80% of C. metapsilosis and C. orthospilosis were misidentified as C. auris. However, previous studies indicated that these species are rarely detected in surveillance screening of C. auris. Naganishia diffluens also resembled C. auris, although it required different temperature growth (30 °C). In conclusion, CHROMagar™ Candida Plus provides rapid presumptive identification of C. auris. It would be another valuable tool in surveillance efforts to control the spread of C. auris in healthcare.

Sugar alcohols derived from lactose: lactitol, galactitol, and sorbitol.

Lactose is a common natural disaccharide composed of galactose and glucose molecules. It is mainly found in the whey, the by-product of cheese and casein industries. As the supply of lactose far exceeds demand, a lot of lactose was discarded as the waste every year, which not only leads to resource waste, but also causes environmental pollution. Therefore, the deep processing of lactose as the feedstock has become a hot research topic. The lactose-derived sugar alcohols, including lactitol, sorbitol, and galactitol, have shown great potential applications not only in food manufacture, but also in pharmaceutical, cosmetic, and material fields. In this paper, we focus on the property, physiological effect, production, and application of the lactose-derived sugar alcohols. KEY POINTS: • The deep processing of lactose as the feedstock has become a hot research topic. • The lactose-derived sugar alcohols show great application values. • Recent advances in the lactose-derived sugar alcohols are reviewed.

Galactitol catabolism in Sinorhizobium meliloti is dependent on a chromosomally encoded sorbitol dehydrogenase and a pSymB-encoded operon necessary for tagatose catabolism.

The legume endosymbiont Sinorhizobium meliloti can utilize a broad range of carbon compounds to support its growth. The linear, six-carbon polyol galactitol is abundant in vascular plants and is metabolized in S. meliloti by the contribution of two loci SMb21372-SMb21377 and SMc01495-SMc01503 which are found on pSymB and the chromosome, respectively. The data suggest that several transport systems, including the chromosomal ATP-binding cassette (ABC) transporter smoEFGK, contribute to the uptake of galactitol, while the adjacent gene smoS encodes a protein for oxidation of galactitol into tagatose. Subsequently, genes SMb21374 and SMb21373, encode proteins that phosphorylate and epimerize tagatose into fructose-6-phosphate, which is further metabolized by the enzymes of the Entner-Doudoroff pathway. Of note, it was found that SMb21373, which was annotated as a 1,6-bis-phospho-aldolase, is homologous to the E. coli gene gatZ, which is annotated as encoding the non-catalytic subunit of a tagatose-1,6-bisphosphate aldolase heterodimer. When either of these genes was introduced into an Agrobacterium tumefaciens strain that carries a tagatose-6-phosphate epimerase mutation, they are capable of complementing the galactitol growth deficiency associated with this mutation, strongly suggesting that these genes are both epimerases. Phylogenetic analysis of the protein family (IPR012062) to which these enzymes belong, suggests that this misannotation is systemic throughout the family. S. meliloti galactitol catabolic mutants do not exhibit symbiotic deficiencies or the inability to compete for nodule occupancy.

In silico screening of sugar alcohol compounds to inhibit viral matrix protein VP40 of Ebola virus.

Ebola virus is a virulent pathogen that causes highly lethal hemorrhagic fever in human and non-human species. The rapid growth of this virus infection has made the scenario increasingly complicated to control the disease. Receptor viral matrix protein (VP40) is highly responsible for the replication and budding of progeny virus. The binding of RNA to VP40 could be the crucial factor for the successful lifecycle of the Ebola virus. In this study, we aimed to identify the potential drug that could inhibit VP40. Sugar alcohols were enrich with antiviral properties used to inhibit VP40. Virtual screening analysis was perform for the 48 sugar alcohol compounds, of which the following three compounds show the best binding affinity: Sorbitol, Mannitol and Galactitol. To understand the perfect binding orientation and the strength of non-bonded interactions, individual molecular docking studies were perform for the best hits. Further molecular dynamics studies were conduct to analyze the efficacy between the protein-ligand complexes and it was identify that Sorbitol obtains the highest efficacy. The best-screened compounds obtained drug-like property and were less toxic, which could be use as a potential lead compound to develop anti-Ebola drugs.

Novel Mutation in GALT Gene in Galactosemia Patient with Group B Streptococcus Meningitis and Acute Liver Failure.

Classic galactosemia is an autosomal recessive disorder caused by the deficiency of the enzyme galactose-1-phosphate uridyltransferase (GALT) involved in galactose metabolism. Bacterial infections are a known cause of early morbidity and mortality in children with classic galactosemia. The most common agent is Escherichia coli, but in rare situations, other bacteria are incriminated. We report a case of a three-week-old female patient with galactosemia, who presented with Group B Streptococcus (GBS) meningitis/sepsis. She received treatment with antibiotics, supportive therapy, and erythrocyte transfusion, but after a short period of improvement, she presented acute liver failure with suspicion of an inborn error of metabolism. Rapid nuclear magnetic resonance (NMR) spectroscopy from urine showed highly elevated values of galactose and galactitol. Under intensive treatment for acute liver failure and with a lactose-free diet, her clinical features and laboratory parameters improved considerably. Genetic testing confirmed compound heterozygous status for GALT mutations: c.563 A>G [p.Q188R] and c. 910 C>T, the last mutation being a novel mutation in GALT gene. In countries without an extensive newborn screening program, a high index of suspicion is necessary for early diagnosis and treatment of galactosemia.

Recurrent Reverse Evolution Maintains Polymorphism after Strong Bottlenecks in Commensal Gut Bacteria.

The evolution of new strains within the gut ecosystem is poorly understood. We used a natural but controlled system to follow the emergence of intraspecies diversity of commensal Escherichia coli, during three rounds of adaptation to the mouse gut (∼1,300 generations). We previously showed that, in the first round, a strongly beneficial phenotype (loss-of-function for galactitol consumption; gat-negative) spread to >90% frequency in all colonized mice. Here, we show that this loss-of-function is repeatedly reversed when a gat-negative clone colonizes new mice. The regain of function occurs via compensatory mutation and reversion, the latter leaving no trace of past adaptation. We further show that loss-of-function adaptive mutants reevolve, after colonization with an evolved gat-positive clone. Thus, even under strong bottlenecks a regime of strong-mutation-strong-selection dominates adaptation. Coupling experiments and modeling, we establish that reverse evolution recurrently generates two coexisting phenotypes within the microbiota that can or not consume galactitol (gat-positive and gat-negative, respectively). Although the abundance of the dominant strain, the gat-negative, depends on the microbiota composition, gat-positive abundance is independent of the microbiota composition and can be precisely manipulated by supplementing the diet with galactitol. These results show that a specific diet is able to change the abundance of specific strains. Importantly, we find polymorphism for these phenotypes in indigenous Enterobacteria of mice and man. Our results demonstrate that natural selection can greatly overwhelm genetic drift at structuring the strain diversity of gut commensals and that competition for limiting resources may be a key mechanism for maintaining polymorphism in the gut.

The Structural Signs of Sweetness in Artificial Sweeteners: A Rotational Study of Sorbitol and Dulcitol.

A gas-phase study on the artificial sweeteners sorbitol and dulcitol has been carried out for the first time by using a combination of chirped-pulse Fourier-transform microwave (CP-FTMW) spectroscopy and laser ablation (LA). The isolation conditions provided by the supersonic expansion reveal the intrinsic conformational structures of these sweeteners. The three and five observed conformers for sorbitol and dulcitol, respectively, are stabilized by networks of cooperative intramolecular hydrogen bonds between vicinal hydroxyl groups in clockwise or counterclockwise arrangements. Suitable places in the structure of seven out of eight conformers identified for both polyalcohols meet the requirements of the glucophore proposed by Shallenberger and Acree's molecular theory of sweet taste. Present results provide the first linkage between sweetness and structure in sugar alcohols.

Genetic Characterization of the Galactitol Utilization Pathway of Salmonella enterica Serovar Typhimurium.

Galactitol degradation by salmonellae remains underinvestigated, although this metabolic capability contributes to growth in animals (R. R. Chaudhuri et al., PLoS Genet 9:e1003456, 2013, https://doi.org/10.1371/journal.pgen.1003456). The genes responsible for this metabolic capability are part of a 9.6-kb gene cluster that spans from gatY to gatR (STM3253 to STM3262) and encodes a phosphotransferase system, four enzymes, and a transporter of the major facilitator superfamily. Genome comparison revealed the presence of this genetic determinant in nearly all Salmonella strains. The generation time of Salmonella enterica serovar Typhimurium strain ST4/74 was higher in minimal medium with galactitol than with glucose. Knockout of STM3254 and gatC resulted in a growth-deficient phenotype of S Typhimurium, with galactitol as the sole carbon source. Partial deletion of gatR strongly reduced the lag phase of growth with galactitol, whereas strains overproducing GatR exhibited a near-zero growth phenotype. Luciferase reporter assays demonstrated strong induction of the gatY and gatZ promoters, which control all genes of this cluster except gatR, in the presence of galactitol but not glucose. Purified GatR bound to these two main gat gene cluster promoters as well as to its own promoter, demonstrating that this autoregulated repressor controls galactitol degradation. Surface plasmon resonance spectroscopy revealed distinct binding properties of GatR toward the three promoters, resulting in a model of differential gat gene expression. The cyclic AMP receptor protein (CRP) bound these promoters with similarly high affinities, and a mutant lacking crp showed severe growth attenuation, demonstrating that galactitol utilization is subject to catabolite repression. Here, we provide the first genetic characterization of galactitol degradation in Salmonella, revealing novel insights into the regulation of this dissimilatory pathway. IMPORTANCE: The knowledge of how pathogens adapt their metabolism to the compartments encountered in hosts is pivotal to our understanding of bacterial infections. Recent research revealed that enteropathogens have adapted specific metabolic pathways that contribute to their virulence properties, for example, by helping to overcome limitations in nutrient availability in the gut due to colonization resistance. The capability of Salmonella enterica serovar Typhimurium to degrade galactitol has already been demonstrated to play a role in vivo, but it has not been investigated so far on the genetic level. To our knowledge, this is the first molecular description of the galactitol degradation pathway of a pathogen.

ATP-binding Cassette (ABC) Transport System Solute-binding Protein-guided Identification of Novel d-Altritol and Galactitol Catabolic Pathways in Agrobacterium tumefaciens C58.

Innovations in the discovery of the functions of uncharacterized proteins/enzymes have become increasingly important as advances in sequencing technology flood protein databases with an exponentially growing number of open reading frames. This study documents one such innovation developed by the Enzyme Function Initiative (EFI; U54GM093342), the use of solute-binding proteins for transport systems to identify novel metabolic pathways. In a previous study, this strategy was applied to the tripartite ATP-independent periplasmic transporters. Here, we apply this strategy to the ATP-binding cassette transporters and report the discovery of novel catabolic pathways for d-altritol and galactitol in Agrobacterium tumefaciens C58. These efforts resulted in the description of three novel enzymatic reactions as follows: 1) oxidation of d-altritol to d-tagatose via a dehydrogenase in Pfam family PF00107, a previously unknown reaction; 2) phosphorylation of d-tagatose to d-tagatose 6-phosphate via a kinase in Pfam family PF00294, a previously orphan EC number; and 3) epimerization of d-tagatose 6-phosphate C-4 to d-fructose 6-phosphate via a member of Pfam family PF08013, another previously unknown reaction. The epimerization reaction catalyzed by a member of PF08013 is especially noteworthy, because the functions of members of PF08013 have been unknown. These discoveries were assisted by the following two synergistic bioinformatics web tools made available by the Enzyme Function Initiative: the EFI-Enzyme Similarity Tool and the EFI-Genome Neighborhood Tool.

Caproiciproducens galactitolivorans gen. nov., sp. nov., a bacterium capable of producing caproic acid from galactitol, isolated from a wastewater treatment plant.

A strictly anaerobic, Gram-stain-positive, non-spore-forming, rod-shaped bacterial strain, designated BS-1T, was isolated from an anaerobic digestion reactor during a study of bacteria utilizing galactitol as the carbon source. Its cells were 0.3-0.5 µm × 2-4 µm, and they grew at 35-45 °C and at pH 6.0-8.0. Strain BS-1T produced H2, CO2, ethanol, acetic acid, butyric acid and caproic acid as metabolic end products of anaerobic fermentation. Phylogenetic analysis, based on the 16S rRNA gene sequence, showed that strain BS-1T represented a novel bacterial genus within the family Ruminococcaceae, Clostridium Cluster IV. The type strains that were most closely related to strain BS-1T were Clostridium sporosphaeroides KCTC 5598T (94.5 %), Clostridium leptum KCTC 5155T (94.3 %), Ruminococcus bromii ATCC 27255T (92.1 %) and Ethanoligenens harbinense YUAN-3T (91.9 %). Strain BS-1T had 17.6 % and 20.9 % DNA-DNA relatedness values with C. sporosphaeroides DSM 1294T and C. leptum DSM 753T, respectively. The major components of the cellular fatty acids were C16 : 0 dimethyl aldehyde (DMA) (22.1 %), C16 : 0 aldehyde (14.1 %) and summed feature 11 (iso-C17 : 0 3-OH and/or C18 : 2 DMA; 10.0 %). The genomic DNA G+C content was 50.0 mol%. Phenotypic and phylogenetic characteristics allowed strain BS-1T to be clearly distinguished from other taxa of the genus Clostridium Cluster IV. On the basis of these data, the isolate is considered to represent a novel genus and novel species within Clostridium Cluster IV, for which the name Caproiciproducens galactitolivorans gen. nov., sp. nov. is proposed. The type species is BS-1T ( = JCM 30532T and KCCM 43048T).

Enhanced production of poly(lactate-co-3-hydroxybutyrate) from xylose in engineered Escherichia coli overexpressing a galactitol transporter.

Poly(lactate-co-3-hydroxybutyrate) (P(LA-co-3HB)) was previously produced from xylose in engineered Escherichia coli. The aim of this study was to increase the polymer productivity and LA fraction in P(LA-co-3HB) using two metabolic engineering approaches: (1) deletions of competing pathways to lactate production and (2) overexpression of a galactitol transporter (GatC), which contributes to the ATP-independent xylose uptake. Engineered E. coli mutants (ΔpflA, Δpta, ΔackA, ΔpoxB, Δdld, and a dual mutant; ΔpflA + Δdld) and their parent strain, BW25113, were grown on 20 g l(-1) xylose for P(LA-co-3HB) production. The single deletions of ΔpflA, Δpta, and Δdld increased the LA fraction (58-66 mol%) compared to BW25113 (56 mol%). In particular, the ΔpflA + Δdld strain produced P(LA-co-3HB) containing 73 mol% LA. Furthermore, GatC overexpression increased both polymer yields and LA fractions in ΔpflA, Δpta, and Δdld mutants, and BW25113. The ΔpflA + gatC strain achieved a productivity of 8.3 g l(-1), which was 72 % of the theoretical maximum yield. Thus, to eliminate limitation of the carbon source, higher concentration of xylose was fed. As a result, BW25113 harboring gatC grown on 40 g l(-1) xylose reached the highest P(LA-co-3HB) productivity of 14.4 g l(-1). On the other hand, the ΔpflA + Δdld strain grown on 30 g l(-1) xylose synthesized 6.4 g l(-1) P(LA-co-3HB) while maintaining the highest LA fraction (73 mol%). The results indicated the usefulness of GatC for enhanced production of P(LA-co-3HB) from xylose, and the gene deletions to upregulate the LA fraction in P(LA-co-3HB). The polymers obtained had weight-averaged molecular weights in the range of 34,000-114,000.

Aldose reductase inhibitors of plant origin.

Diabetic complications are attributed to hyperglycaemic condition which is in turn associated with the polyol pathway and advanced glycation end products. Aldose reductase (AR) is the principal enzyme of polyol pathway which plays a vital role in the development of diabetic complications. AR inhibitory activity can be screened by both in vitro and in vivo methods. In vitro assays for AR enzyme are further classified on the basis of the source of enzyme such as rat lens, rat kidney, cataracted human eye lens, bovine eyes and human recombinant AR enzymes, whereas the in vivo model is based on the determination of lens galactitol levels. A number of synthetic AR inhibitors (ARIs) including tolrestat and sorbinil have been developed, but all of these suffer from drawbacks such as poor permeation and safety issues. Therefore, pharmaceutical companies and many researchers have been carrying out research to find new, potent and safe ARIs from natural sources. Thus, many naturally occurring compounds have been reported to have AR inhibitory activity. The present review attempts to highlight phytochemicals and plant extracts with potential AR inhibitory activity. It also summarizes the classes of compounds which have proven AR inhibitory activity. Phytochemicals such as quercetin, kaempferol and ellagic acid are found to be the most promising ARIs. The exhaustive literature presented in this article clearly indicates the role of plant extracts and phytochemicals as potential ARIs.

[Construction and culture condition optimization of a Saccharomyces cerevisiae strain for production of galactitol].

Galactitol, a rare sugar alcohol, has promising potential in the food industry and pharmaceutical field. The available industrial production methods rely on harsh hydrogenation processes, which incur high costs and environmental concerns. It is urgent to develop environmentally friendly and efficient biosynthesis technologies. In this study, a xylose reductase named AnXR derived from Aspergillus niger CBS 513.88 was identified and characterized for the enzymatic properties. AnXR exhibited the highest activity at 25 ℃ and pH 8.0, and it belonged to the NADPH-dependent aldose reductase family. To engineer a strain for galactitol production, we deleted the galactokinase (GAL1) gene in Saccharomyes cerevisiae by using the recombinant gene technology, which significantly reduced the metabolic utilization of D-galactose by host cells. Subsequently, we introduced the gene encoding AnXR into this modified strain, creating an engineered strain capable of catalyzing the conversion of D-galactose into galactitol. Furthermore, we optimized the whole-cell catalysis conditions for the engineered strain, which achieved a maximum galactitol yield of 12.10 g/L. Finally, we tested the reduction ability of the strain for other monosaccharides and discovered that it could produce functional sugar alcohols such as xylitol and arabinitol. The engineered strain demonstrates efficient biotransformation capabilities for galactitol and other functional sugar alcohols, representing a significant advancement in environmentally sustainable production practices.

Low molecular weight carbohydrate patterns of mangrove macroalgae from different climatic niches under ocean acidification, warming and salinity variation.

Ocean acidification has increased due to the enhanced solubility of CO2 in seawater. Mangrove macroalgae in tropical and subtropical coastal regions can benefit from the higher availability of CO2 for photosynthesis and primary production. However, they can be negatively affected by the simultaneously occurring warming and increased salinity in estuaries. Thus, we analyzed the isolated effects of ocean acidification and the interactive effects of increased temperature and salinity on the low molecular weight carbohydrate (LMWC) contents of the mangrove red macroalgae Bostrychia montagnei and Bostrychia calliptera from Brazilian tropical and subtropical populations. Specimens from both climatic niches were tolerant to pH decreased by CO2 enrichment and enhanced their LMWC contents under increased availability of CO2. Specimens from both climatic niches also accumulated their dulcitol and sorbitol contents to cope with warming and salt stress. Nevertheless, temperature of 34 °C was lethal for tropical macroalgae, while 29 °C and 31 °C were lethal for subtropical B. calliptera under salinity of 35. Tropical and subtropical B. montagnei synthesized dulcitol (5-110 mmol kg-1 dry weight) and sorbitol (5-100 mmol kg-1 dry weight) as osmoregulatory, energy and thermal protection compounds, whereas tropical and subtropical B. calliptera synthesized mainly dulcitol (10-210 mmol kg-1 dry weight). Although digeneaside has an energy function in Bostrychia spp., it is not an osmolyte or thermal protection compound. Our data demonstrated that both tropical and subtropical Bostrychia spp. benefit from ocean acidification by CO2 enrichment, increasing their LMWC contents. However, warming and increased salinity in estuaries will be detrimental to them, even they producing protective metabolites. Multifactorial approaches are recommended to investigate whether negative effects of increased temperature and salinity nullify positive effects of ocean acidification on these Bostrychia species/populations.

Early diet impacts infant rhesus gut microbiome, immunity, and metabolism.

Epidemiological research has indicated a relationship between infant formula feeding and increased risk of chronic diseases later in life including obesity, type-2 diabetes, and cardiovascular disease. The present study used an infant rhesus monkey model to compare the comprehensive metabolic implications of formula- and breast-feeding practices using NMR spectroscopy to characterize metabolite fingerprints from urine and serum, in combination with anthropometric measurements, fecal microbial profiling, and cytokine measurements. Here we show that formula-fed infants are larger than their breast-fed counterparts and have a different gut microbiome that includes higher levels of bacteria from the Ruminococcus genus and lower levels of bacteria from the Lactobacillus genus. In addition, formula-fed infants have higher serum insulin coupled with higher amino acid levels, while amino acid degradation products were higher in breast-fed infants. Increases in serum and urine galactose and urine galactitol were observed in the second month of life in formula-fed infants, along with higher levels of TNFα, IFN-γ, IL-1ß, IL-4, and other cytokines and growth factors at week 4. These results demonstrate that metabolic and gut microbiome development of formula-fed infants is different from breast-fed infants and that the choice of infant feeding may hold future health consequences.

Aldose reductase inhibitor counteracts the enhanced expression of matrix metalloproteinase-10 and improves corneal wound healing in galactose-fed rats.

PURPOSE: We investigated the effect of an aldose reductase inhibitor (ARI) and the role of matrix metalloproteinase (MMP)-10 on recovery after corneal epithelium removal in a rat diabetic keratopathy model. METHODS: Three-week-old Sprague-Dawley rats were fed the following diets for 6 weeks: normal MF chow (MF), 50% galactose (Gal), and 50% Gal containing 0.01% ARI (Gal +ARI). The corneal epithelium was removed using n-heptanol, and the area of epithelial defects was photographed and measured every 24 h. Real-time reverse transcriptase PCR, western blotting, and immunohistochemistry were used to determine the expression profile of MMP-10 and integrin α3. RESULTS: Compared to the MF control group, the amount of galactitol in the Gal group increased approximately 200-fold, which was reduced to sevenfold by ARI treatment. The area of corneal erosion in the Gal group was significantly larger than in the MF group at 72 h and thereafter (p<0.01, unpaired t test). The expression level of MMP-10 was enhanced at both the protein and mRNA levels by exposure to a high concentration of Gal, while integrin α3 expression decreased at the protein level but remained unchanged at the mRNA level. Delayed epithelial wound healing and alterations in the expression levels of MMP-10 and integrin α3 were normalized by ARI. The corneal erosion closure rate was significantly decreased with topical recombinant MMP-10. CONCLUSIONS: These studies confirm that the increased expression of MMP-10 induced by Gal feeding is counteracted by ARI treatment and suggest a role of MMP-10 in modulating corneal epithelial wound healing.

Proton fingerprints portray molecular structures: enhanced description of the 1H NMR spectra of small molecules.

The characteristic signals observed in NMR spectra encode essential information on the structure of small molecules. However, extracting all of this information from complex signal patterns is not trivial. This report demonstrates how computer-aided spectral analysis enables the complete interpretation of 1D (1)H NMR data. The effectiveness of this approach is illustrated with a set of organic molecules, for which replicas of their (1)H NMR spectra were generated. The potential impact of this methodology on organic chemistry research is discussed.