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The behavior of polar LaMnO3 (LMO) thin films deposited epitaxially on nonpolar SrTiO3(001) (STO) is dictated by both the LMO/STO band alignment and the chemistry of the Mn cation. Using in situ X-ray photoelectron spectroscopy, the valence band offset (VBO) of LMO/STO heterojunctions is directly measured as a function of thickness, and found that the VBO is 2.5 eV for thicker (≥3 u.c.) films. No evidence of a built-in electric field in LMO films of any thickness is found. Measurements of the Mn valence by Mn L-edge X-ray absorption spectroscopy and by spatially resolved electron energy loss spectra in scanning transmission electron microscopy images reveal that Mn2+ is present at the LMO surface, but not at the LMO/STO interface. These results are corroborated by density functional theory simulations that confirm a VBO of ≈2.5 eV for both ideal and intermixed interfaces. A model is proposed for the behavior of polar/nonpolar LMO/STO heterojunctions in which the polar catastrophe is alleviated by the formation of oxygen vacancies at the LMO surface.

LaCrO3(LCO)/SrTiO3(STO) heterojunctions are intriguing due to a polar discontinuity along [001], exhibiting two distinct and controllable charged interface structures [(LaO)+/(TiO2)0 and (SrO)0/(CrO2)-] with induced polarization, and a resulting depth-dependent potential. In this study, we have used soft- and hard-x-ray standing-wave excited photoemission spectroscopy (SW-XPS) to quantitatively determine the elemental depth profile, interface properties, and depth distribution of the polarization-induced built-in potentials. We observe an alternating charged interface configuration: a positively charged (LaO)+/(TiO2)0 intermediate layer at the LCOtop/STObottom interface and a negatively charged (SrO)0/(CrO2)- intermediate layer at the STOtop/LCObottom interface. Using core-level SW data, we have determined the depth distribution of species, including through the interfaces, and these results are in excellent agreement with scanning transmission electron microscopy and electron energy-loss spectroscopy mapping of local structure and composition. SW-XPS also enabled deconvolution of the LCO and STO contributions to the valence-band (VB) spectra. Using a two-step analytical approach involving first SW-induced core-level binding-energy shifts and then VB modeling, the variation in potential across the complete superlattice is determined in detail. This potential is in excellent agreement with density functional theory models, confirming this method as a generally useful tool for interface studies.

LaCrO3(LCO)/SrTiO3(STO) heterojunctions are intriguing due to a polar discontinuity along [001], exhibiting two distinct and controllable charged interface structures [(LaO)+/(TiO2)0 and (SrO)0/(CrO2)-] with induced polarization, and a resulting depth-dependent potential. In this study, we have used soft- and hard-x-ray standing-wave excited photoemission spectroscopy (SW-XPS) to quantitatively determine the elemental depth profile, interface properties, and depth distribution of the polarization-induced built-in potentials. We observe an alternating charged interface configuration: a positively charged (LaO)+/(TiO2)0 intermediate layer at the LCOtop/STObottom interface and a negatively charged (SrO)0/(CrO2)- intermediate layer at the STOtop/LCObottom interface. Using core-level SW data, we have determined the depth distribution of species, including through the interfaces, and these results are in excellent agreement with scanning transmission electron microscopy and electron energy-loss spectroscopy mapping of local structure and composition. SW-XPS also enabled deconvolution of the LCO and STO contributions to the valence-band (VB) spectra. Using a two-step analytical approach involving first SW-induced core-level binding-energy shifts and then VB modeling, the variation in potential across the complete superlattice is determined in detail. This potential is in excellent agreement with density functional theory models, confirming this method as a generally useful tool for interface studies.

Perovskite titanates such as SrTiO3 (STO) exhibit a wide range of important functional properties, including ferroelectricity and excellent photocatalytic performance. The wide optical band gap of titanates limits their use in these applications; however, making them ill-suited for integration into solar energy harvesting technologies. Our recent work has shown that by doping STO with equal concentrations of La and Cr, we can enhance visible light absorption in epitaxial thin films while avoiding any compensating defects. In this work, we explore the optical properties of photoexcited carriers in these films. Using spectroscopic ellipsometry, we show that the Cr3+ dopants, which produce electronic states immediately above the top of the O 2p valence band in STO reduce the direct band gap of the material from 3.75 eV to 2.4-2.7 eV depending on doping levels. Transient reflectance spectroscopy measurements are in agreement with the observations from ellipsometry and confirm that optically generated carriers are present for longer than 2 ns. Finally, through photoelectrochemical methylene blue degradation measurements, we show that these co-doped films exhibit enhanced visible light photocatalysis when compared to pure STO.

Charge transfer or redistribution at oxide heterointerfaces is a critical phenomenon, often leading to remarkable properties such as two-dimensional electron gas and interfacial ferromagnetism. Despite studies on LaNiO 3 /LaFeO 3 superlattices and heterostructures, the direction and magnitude of the charge transfer remain debated, with some suggesting no charge transfer due to the high stability of Fe 3+ (3d 5 ). Here, we synthesized a series of epitaxial LaNiO 3 /LaFeO 3 superlattices and demonstrated partial (up to ~0.5 e - /interface unit cell) charge transfer from Fe to Ni near the interface, supported by density functional theory simulations and spectroscopic evidence of changes in Ni and Fe oxidation states. The electron transfer from LaFeO 3 to LaNiO 3 and the subsequent rearrangement of the Fe 3d band create an unexpected metallic ground state within the LaFeO 3 layer, strongly influencing the in-plane transport properties across the superlattice. Moreover, we establish a direct correlation between interfacial charge transfer and in-plane electrical transport properties, providing insights for designing functional oxide heterostructures with emerging properties.

Phosphoethanolamine (pEtN) cellulose is a naturally occurring modified cellulose produced by several Enterobacteriaceae. The minimal components of the E. coli cellulose synthase complex include the catalytically active BcsA enzyme, a hexameric semicircle of the periplasmic BcsB protein, and the outer membrane (OM)-integrated BcsC subunit containing periplasmic tetratricopeptide repeats (TPR). Additional subunits include BcsG, a membrane-anchored periplasmic pEtN transferase associated with BcsA, and BcsZ, a periplasmic cellulase of unknown biological function. While cellulose synthesis and translocation by BcsA are well described, little is known about its pEtN modification and translocation across the cell envelope. We show that the N-terminal cytosolic domain of BcsA positions three BcsG copies near the nascent cellulose polymer. Further, the semicircle's terminal BcsB subunit tethers the N-terminus of a single BcsC protein in a trans-envelope secretion system. BcsC's TPR motifs bind a putative cello-oligosaccharide near the entrance to its OM pore. Additionally, we show that only the hydrolytic activity of BcsZ but not the subunit itself is necessary for cellulose secretion, suggesting a secretion mechanism based on enzymatic removal of translocation incompetent cellulose. Lastly, protein engineering introduces cellulose pEtN modification in orthogonal cellulose biosynthetic systems. These findings advance our understanding of pEtN cellulose modification and secretion., (© 2024. The Author(s).)

Phosphoethanolamine (pEtN) cellulose is a naturally occurring modified cellulose produced by several Enterobacteriaceae. The minimal components of the E. coli cellulose synthase complex include the catalytically active BcsA enzyme, an associated periplasmic semicircle of hexameric BcsB, as well as the outer membrane (OM)-integrated BcsC subunit containing periplasmic tetratricopeptide repeats (TPR). Additional subunits include BcsG, a membrane-anchored periplasmic pEtN transferase associated with BcsA, and BcsZ, a conserved periplasmic cellulase of unknown biological function. While events underlying the synthesis and translocation of cellulose by BcsA are well described, little is known about its pEtN modification and translocation across the cell envelope. We show that the N-terminal cytosolic domain of BcsA positions three copies of BcsG near the nascent cellulose polymer. Further, the terminal subunit of the BcsB semicircle tethers the N-terminus of a single BcsC protein to establish a trans-envelope secretion system. BcsC's TPR motifs bind a putative cello-oligosaccharide near the entrance to its OM pore. Additionally, we show that only the hydrolytic activity of BcsZ but not the subunit itself is necessary for cellulose secretion, suggesting a secretion mechanism based on enzymatic removal of mislocalized cellulose. Lastly, we introduce pEtN modification of cellulose in orthogonal cellulose biosynthetic systems by protein engineering., Competing Interests: Conflict of interest The authors declare no conflict of interests.

Exposure to environmental toxicants (such as dioxins) has been epidemiologically linked to adverse reproductive health outcomes, including placental inflammation and preterm birth. However, the molecular underpinnings that govern these outcomes in gravid reproductive tissues remain largely unclear. Placental macrophages (also known as Hofbauer cells) are crucial innate immune cells that defend the gravid reproductive tract and help promote maternal-fetal tolerance. We hypothesized that exposure to environmental toxicants such as 2,3,7,8-tetrachlorodibenzo- p -dioxin (TCDD) could alter placental macrophage responses to inflammatory insults such as infection. To test this, placental macrophages were cultured in the presence or absence of TCDD and then infected with the perinatal pathogen Group B Streptococcus (GBS). Our results indicate that TCDD is lethal to placental macrophages at and above a 5 nM concentration and that sublethal dioxin exposure inhibits phagocytosis and cytokine production. Taken together, these results indicate that TCDD paralyzes placental macrophage responses to bacterial infection.

Anisotropic and efficient transport of ions under external stimuli governs the operation and failure mechanisms of energy-conversion systems and microelectronics devices. However, fundamental understanding of ion hopping processes is impeded by the lack of atomically precise materials and probes that allow for the monitoring and control at the appropriate time- and length- scales. In this work, using in-situ transmission electron microscopy, we directly show that oxygen ion migration in vacancy ordered, semiconducting SrFeO 2.5 epitaxial thin films can be guided to proceed through two distinctly different diffusion pathways, each resulting in different polymorphs of SrFeO 2.75 with different ground electronic properties before reaching a fully oxidized, metallic SrFeO 3 phase. The diffusion steps and reaction intermediates are revealed by means of ab-initio calculations. The principles of controlling oxygen diffusion pathways and reaction intermediates demonstrated here may advance the rational design of structurally ordered oxides for tailored applications and provide insights for developing devices with multiple states of regulation., (© 2023. Springer Nature Limited.)

Escherichia coli and other Enterobacteriaceae thrive in robust biofilm communities through the coproduction of curli amyloid fibers and phosphoethanolamine cellulose. Curli promote adhesion to abiotic surfaces and plant and human host tissues and are associated with pathogenesis in urinary tract infection and food-borne illness. The production of curli in the host has also been implicated in the pathogenesis of neurodegenerative diseases. We report that the natural product nordihydroguaiaretic acid (NDGA) is effective as a curlicide in E. coli. NDGA prevents CsgA polymerization in vitro in a dose-dependent manner. NDGA selectively inhibits cell-associated curli assembly and inhibits uropathogenic E. coli biofilm formation. More broadly, this work emphasizes the ability to evaluate and identify bioactive amyloid assembly inhibitors by using the powerful gene-directed amyloid biogenesis machinery in E. coli., (© 2023 Wiley-VCH GmbH.)

Preterm birth affects nearly 10% of all pregnancies in the United States, with 40% of those due, in part, to infections. Streptococcus agalactiae (Group B Streptococcus , GBS) is one of the most common perinatal pathogens responsible for these infections. Current therapeutic techniques aimed to ameliorate invasive GBS infections are less than desirable and can result in complications in both the neonate and the mother. To this end, the need for novel therapeutic options is urgent. Human milk oligosaccharides (HMOs), an integral component of human breast milk, have been previously shown to possess antiadhesive and antimicrobial properties. To interrogate these characteristics, we examined HMO-mediated outcomes in both in vivo and ex vivo models of GBS infection utilizing a murine model of ascending GBS infection, an EpiVaginal human organoid tissue model, and ex vivo human gestational membranes. Supplementation of HMOs resulted in diminished adverse pregnancy outcomes, decreased GBS adherence to gestational tissues, decreased colonization within the reproductive tract, and reduced proinflammatory immune responses to GBS infection. Taken together, these results highlight the potential of HMOs as promising therapeutic interventions in perinatal health., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Water electrolysis can use renewable electricity to produce green hydrogen, a portable fuel and sustainable chemical precursor. Improving electrolyzer efficiency hinges on the activity of the oxygen evolution reaction (OER) catalyst. Earth-abundant, ABO 3 -type perovskite oxides offer great compositional, structural, and electronic tunability, with previous studies showing compositional substitution can increase the OER activity drastically. However, the relationship between the tailored bulk composition and that of the surface, where OER occurs, remains unclear. Here, we study the effects of electrochemical cycling on the OER activity of La 0.5 Sr 0.5 Ni 1- x Fe x O 3- δ ( x = 0-0.5) epitaxial films grown by oxide molecular beam epitaxy as a model Sr-containing perovskite oxide. Electrochemical testing and surface-sensitive spectroscopic analyses show Ni segregation, which is affected by electrochemical history, along with surface amorphization, coupled with changes in OER activity. Our findings highlight the importance of surface composition and electrochemical cycling conditions in understanding OER performance, suggesting common motifs of the active surface with high surface area systems.

The epitaxial growth of functional oxides using a substrate with a graphene layer is a highly desirable method for improving structural quality and obtaining freestanding epitaxial nanomembranes for scientific study, applications, and economical reuse of substrates. However, the aggressive oxidizing conditions typically used in growing epitaxial oxides can damage graphene. Here, we demonstrate the successful use of hybrid molecular beam epitaxy for SrTiO 3 growth that does not require an independent oxygen source, thus avoiding graphene damage. This approach produces epitaxial films with self-regulating cation stoichiometry. Furthermore, the film (46-nm-thick SrTiO 3 ) can be exfoliated and transferred to foreign substrates. These results open the door to future studies of previously unattainable freestanding oxide nanomembranes grown in an adsorption-controlled manner by hybrid molecular beam epitaxy. This approach has potentially important implications for the commercial application of perovskite oxides in flexible electronics and as a dielectric in van der Waals thin-film electronics.

Plasmons in strongly correlated systems are attracting considerable attention due to their unconventional behavior caused by electronic correlation effects. Recently, flat plasmons with nearly dispersionless frequency-wave vector relations have drawn significant interest because of their intriguing physical origin and promising applications. However, these flat plasmons exist primarily in low-dimensional materials with limited wave vector magnitudes (q < ~0.7 Å -1 ). Here, we show that long-lived flat plasmons can propagate up to ~1.2 Å -1 in α-Ti 2 O 3 , a strongly correlated three-dimensional Mott-insulator, with an ultra-small energy fluctuation (<40 meV). The strong correlation effect renormalizes the electronic bands near Fermi level with a small bandwidth, which is responsible for the flat plasmons in α-Ti 2 O 3 . Moreover, these flat plasmons are not affected by Landau damping over a wide range of wave vectors (q < ~1.2 Å -1 ) due to symmetry constrains on the electron wavefunctions. Our work provides a strategy for exploring flat plasmons in strongly correlated systems, which in turn may give rise to novel plasmonic devices in which flat and long-lived plasmons are desirable., (© 2022. The Author(s).)

Epitaxial growth is a powerful tool for synthesizing heterostructures and integrating multiple functionalities. However, interfacial mixing can readily occur and significantly modify the properties of layered structures, particularly for those containing energy storage materials with smaller cations. Here, we show a two-step sequence involving the growth of an epitaxial LiCoO 2 cathode layer followed by the deposition of a binary transition metal oxide. Orientation-controlled epitaxial synthesis of the model solid-state-electrolyte Li 2 WO 4 and anode material Li 4 Ti 5 O 12 occurs as WO 3 and TiO 2 nucleate and react with Li ions from the underlying cathode. We demonstrate that this lithiation-assisted epitaxy approach can be used for energy materials discovery and exploring different combinations of epitaxial interfaces that can serve as well-defined model systems for mechanistic studies of energy storage and conversion processes.

Background: Endolymphatic hydrops (EH) has been observed in both animal and human cochleae following cochlear implant (CI) surgery. We tested whether EH could be eliminated by administration of mineralocorticoid steroid antagonist spironolactone and explored the electrophysiological consequences of this., Methods: Sixty-four adult guinea pigs underwent cochlear implantation with a dummy electrode. Animals then survived either 2, 7, or 28 days. Auditory function was monitored by recording electrocochleography from the round window membrane preimplantation, and on the last day of the experiment. Spironolactone or control solution was added to animals' feed for 7 days (if they survived that long) beginning immediately prior to surgery. The presence of EH was determined using thin-sheet laser imaging microscopy., Results: Treatment with spironolactone resulted in significant reduction in EH in the second cochlear turn 7 days postimplantation. In all animals, the compound action potential (CAP) threshold was elevated 2 days postimplantation, but for most frequencies had recovered substantially by 28 days. There was no treatment effect on CAP thresholds. SP/AP ratios were elevated at day 2. The amplitude growth of the CAP did not differ between test and control groups at any time after implantation., Conclusions: EH can be suppressed by antagonism of mineralocorticoid receptors in the week after cochlear implantation. Reduction in EH did not lead to any change in hearing, and there was no indication of synaptopathy signalled by reduced CAP amplitude at high sound intensities. We found no electrophysiological evidence that EH early after implantation impacts negatively upon preservation of residual hearing., Competing Interests: The authors disclose no conflict of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of Otology & Neurotology, Inc.)

SignificanceSemiconductor interfaces are among the most important in use in modern technology. The properties they exhibit can either enable or disable the characteristics of the materials they connect for functional performance. While much is known about important junctions involving conventional semiconductors such as Si and GaAs, there are several unsolved mysteries surrounding interfaces between oxide semiconductors. Here we resolve a long-standing issue concerning the measurement of anomalously low dielectric constants in SrTiO 3 films with record high electron mobilities. We show that the junction between doped and undoped SrTiO 3 required to make dielectric constant measurements masks the dielectric properties of the undoped film. Through modeling, we extract the latter and show that it is much higher than previously measured.

In many families grandparents play an essential role by providing secondary care for grandchildren. The family is a key setting for promoting children's health; however, studies describing health initiatives with grandparents are rare. Grandparents could play an important role in promoting health for their grandchildren within their families and communities. The aim of this study was to examine the care practices of grandparents in families living in areas of high deprivation, and to consider the extent to which grandparents could be at the centre of health-promoting initiatives for children. A family practices approach was used to examine care practices within the framework of family resource (assets/capitals) use. In-depth interviews were carried out with grandmothers (n = 15) and mothers (n = 15) living in areas of high deprivation in Scotland. The results are presented as three economies of family living-political, moral and emotional. Grandparent care was described as a form of social capital, central to the wellbeing of the families, and enabled parents to access education and employment. Grandparent care was supported through families' ability to access cultural amenities and green space (political). Grandparents' care practices were described as either being responsible or fun (moral). Love appeared to be at the centre of grandparents' care (emotional). The strengths and weaknesses of this framework were examined in relation to developing initiatives with grandparents. With further development work, grandparents could be the focus of health initiatives with their grandchildren with the support of appropriate policies and resources within their communities., (© The Author(s) 2021. Published by Oxford University Press.)

Heterointerfaces have led to the discovery of novel electronic and magnetic states because of their strongly entangled electronic degrees of freedom. Single-phase chromium compounds always exhibit antiferromagnetism following the prediction of the Goodenough-Kanamori rules. So far, exchange coupling between chromium ions via heteroanions has not been explored and the associated quantum states are unknown. Here, we report the successful epitaxial synthesis and characterization of chromium oxide (Cr&#95;{2}O&#95;{3})-chromium nitride (CrN) superlattices. Room-temperature ferromagnetic spin ordering is achieved at the interfaces between these two antiferromagnets, and the magnitude of the effect decays with increasing layer thickness. First-principles calculations indicate that robust ferromagnetic spin interaction between Cr^{3+} ions via anion-hybridization across the interface yields the lowest total energy. This work opens the door to fundamental understanding of the unexpected and exceptional properties of oxide-nitride interfaces and provides access to hidden phases at low-dimensional quantum heterostructures.

Rare earth nickelates including LaNiO 3 are promising catalysts for water electrolysis to produce oxygen gas. Recent studies report that Fe substitution for Ni can significantly enhance the oxygen evolution reaction (OER) activity of LaNiO 3 . However, the role of Fe in increasing the activity remains ambiguous, with potential origins that are both structural and electronic in nature. On the basis of a series of epitaxial LaNi 1- x Fe x O 3 thin films synthesized by molecular beam epitaxy, we report that Fe substitution tunes the Ni oxidation state in LaNi 1- x Fe x O 3 and a volcano-like OER trend is observed, with x = 0.375 being the most active. Spectroscopy and ab initio modeling reveal that high-valent Fe 3+δ cationic species strongly increase the transition-metal (TM) 3d bandwidth via Ni-O-Fe bridges and enhance TM 3d-O 2p hybridization, boosting the OER activity. These studies deepen our understanding of structural and electronic contributions that give rise to enhanced OER activity in perovskite oxides.

Group B Streptococcus (GBS) is one of the leading infection-related causes of adverse maternal and neonatal outcomes. This includes chorioamnionitis, which leads to preterm ruptures of membranes and can ultimately result in preterm or stillbirth. Infection can also lead to maternal and neonatal sepsis that may contribute to mortality. Currently, treatment for GBS infection include a bolus of intrapartum antibiotic prophylaxis to mothers testing positive for GBS colonization during late pregnancy. Lactoferrin is an antimicrobial peptide expressed in human breast milk, mucosal epithelia, and secondary granules of neutrophils. We previously demonstrated that lactoferrin possesses antimicrobial and antibiofilm properties against several strains of GBS. This is largely due to the ability of lactoferrin to bind and sequester iron. We expanded upon that study by assessing the effects of purified human breast milk lactoferrin against a panel of phenotypically and genetically diverse isolates of GBS. Of the 25 GBS isolates screened, lactoferrin reduced bacterial growth in 14 and biofilm formation in 21 strains. Stratifying the data, we observed that colonizing strains were more susceptible to the growth inhibition activity of lactoferrin than invasive isolates at lactoferrin concentrations between 250-750 µg/mL. Treatment with 750 µg/mL of lactoferrin resulted in differences in bacterial growth and biofilm formation between discrete sequence types. Differences in bacterial growth were also observed between capsular serotypes 1a and III. Maternally isolated strains were more susceptible to lactoferrin with respect to bacterial growth, but not biofilm formation, compared to neonatal sepsis isolates. Finally, high biofilm forming GBS strains were more impacted by lactoferrin across all isolates tested. Taken together, this study demonstrates that lactoferrin possesses antimicrobial and antibiofilm properties against a wide range of GBS isolates, with maternally isolated colonizing strains being the most susceptible., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Lu, Guevara, Francis, Spicer, Moore, Chambers, Craft, Manning, Townsend and Gaddy.)

Chronic infection with Helicobacter pylori increases risk of gastric diseases including gastric cancer. Despite development of a robust immune response, H. pylori persists in the gastric niche. Progression of gastric inflammation to serious disease outcomes is associated with infection with H. pylori strains which encode the cag Type IV Secretion System (cag T4SS). The cag T4SS is responsible for translocating the oncogenic protein CagA into host cells and inducing pro-inflammatory and carcinogenic signaling cascades. Our previous work demonstrated that nutrient iron modulates the activity of the T4SS and biogenesis of T4SS pili. In response to H. pylori infection, the host produces a variety of antimicrobial molecules, including the iron-binding glycoprotein, lactoferrin. Our work shows that apo-lactoferrin exerts antimicrobial activity against H. pylori under iron-limited conditions, while holo-lactoferrin enhances bacterial growth. Culturing H. pylori in the presence of holo-lactoferrin prior to co-culture with gastric epithelial cells, results in repression of the cag T4SS activity. Concomitantly, a decrease in biogenesis of cag T4SS pili at the host-pathogen interface was observed under these culture conditions by high-resolution electron microscopy analyses. Taken together, these results indicate that acquisition of alternate sources of nutrient iron plays a role in regulating the pro-inflammatory activity of a bacterial secretion system and present novel therapeutic targets for the treatment of H. pylori-related disease., (© 2021 Wiley-VCH GmbH.)

Group B Streptococcus (GBS) is an encapsulated Gram-positive pathogen that causes ascending infections of the reproductive tract during pregnancy. The capsule of this organism is a critical virulence factor that has been implicated in a variety of cellular processes to promote pathogenesis. Primarily comprised of carbohydrates, the GBS capsule and its synthesis is driven by the c apsule p olysaccharide s ynthesis ( cps ) operon. The cpsE gene within this operon encodes a putative glycosyltransferase that is responsible for the transfer of a Glc-1-P from UDP-Glc to an undecaprenyl lipid molecule. We hypothesized that the cpsE gene product is important for GBS virulence and ascending infection during pregnancy. Our work demonstrates that a GBS cpsE mutant secretes fewer carbohydrates, has a reduced capsule, and forms less biofilm than the wild-type parental strain. We show that, compared to the parental strain, the ΔcpsE deletion mutant is more readily taken up by human placental macrophages and has a significantly attenuated ability to invade and proliferate in the mouse reproductive tract. Taken together, these results demonstrate that the cpsE gene product is an important virulence factor that aids in GBS colonization and invasion of the gravid reproductive tract.

Acinetobacter baumannii is an opportunistic bacterial pathogen that causes severe infections in immunocompromised patients. The emergence of multi- and pan-drug resistant strains of A. baumannii from clinical sources has confounded treatment and enhanced morbidity and mortality associated with these infections. One way that A. baumannii circumnavigates environmental and antimicrobial challenge is by forming tertiary architectural structures of cells known as biofilms. Biofilm-inhibiting molecules could be deployed as a potential chemotherapeutic strategy to inhibit or disrupt A. baumannii biofilms and mitigate adverse outcomes due to infection. Lactoferrin is an innate immune glycoprotein produced in high concentrations in both human and bovine milk which has previously been shown to have antibacterial and antibiofilm activities. We sought to test lactoferrin against a bank of clinical isolates of A. baumannii to determine changes in bacterial growth or biofilm formation. Our results indicate that human lactoferrin has slightly more potent antibacterial activities than bovine lactoferrin against certain strains of A. baumannii and that these effects are associated with anatomical site of isolation. Additionally, we have shown that both bovine and human lactoferrin can inhibit A. baumannii biofilm formation and that these effects are associated with anatomical site of isolation and whether the strain forms robust or weak biofilms.

The discovery of chimeric anti-melanoma agents is reported. These molecules are potent growth suppressors of melanoma cells in vitro with growth inhibition of 50% (GI 50 ) values as low as 1.32 µM. Compounds were more toxic to melanoma cells in vitro than commonly used anti-melanoma agent dacarbazine as measured by TUNEL assay. They induced both caspase-independent apoptosis evident by colocalization of TUNEL with endonuclease G (EndoG) and caspase-mediated apoptosis measured by colocalization of TUNEL with caspase-activated DNase (CAD). In addition, compounds 3 and 5 strongly induced oxidative injury to melanoma cells as measured by TUNEL colocalization with heme oxygenase-1 (HO1). Dacarbazine induced only caspase-independent apoptosis, which may explain why it is less cytotoxic to melanoma cells than compounds 3 , 4 and 5 ., (© 2021 The Authors.)

The titanomagnetites (Fe 2- x Ti x O 4 , x ⩽ 1) are a family of reducible spinel-structure oxides of interest for their favorable magnetic, catalytic, and electrical transport properties. To understand the stability of the system during low temperature deposition, epitaxial thin films of Fe 2 TiO 4 were deposited by molecular beam epitaxy (MBE) on MgO(001) at 250-375 °C. The homogeneous incorporation of Ti, Fe valence state, and film morphology were all found to be strongly dependent on the oxidation conditions at the low substrate temperatures employed. More oxidizing conditions led to phase separation into epitaxial, faceted Fe 3 O 4 and rutile TiO 2 . Less oxidizing conditions resulted in polycrystalline films that exhibited Ti segregation to the film surface, as well as mixed Fe valence (Fe 3+ , Fe 2+ , Fe 0 ). A narrow window of intermediate oxygen partial pressure during deposition yielded nearly homogeneous Ti incorporation and a large fraction of Fe 2+ . However, these films were poorly crystallized, and no occupation of tetrahedral sites in the spinel lattice by Fe 2+ was detected by x-ray magnetic circular dichroism at the Fe L-edge. After vacuum annealing, a small fraction of Fe 2+ was found to occupy tetrahedral sites. Comparison of these results with previous work suggests that the low temperature deposition conditions imposed by use of MgO substrates limits the incorporation of Ti into the spinel lattice. This work suggests a path towards obtaining stoichiometric, well-crystallized Fe 2 TiO 4 by MBE by utilizing high substrate temperature and low oxygen partial pressure during deposition on thermally stable substrates., (© 2021 IOP Publishing Ltd.)

Group B Streptococcus (GBS) is an encapsulated Gram-positive human pathogen that causes invasive infections in pregnant hosts and neonates, as well as immunocompromised individuals. Colonization of the human host requires the ability to adhere to mucosal surfaces and circumnavigate the nutritional challenges and antimicrobial defenses associated with the innate immune response. Biofilm formation is a critical process to facilitate GBS survival and establishment of a replicative niche in the vertebrate host. Previous work has shown that the host responds to GBS infection by producing the innate antimicrobial glycoprotein lactoferrin, which has been implicated in repressing bacterial growth and biofilm formation. Additionally, lactoferrin is highly abundant in human breast milk and could serve a protective role against invasive microbial pathogens. This study demonstrates that human breast milk lactoferrin has antimicrobial and anti-biofilm activity against GBS and inhibits its adherence to human gestational membranes. Together, these results indicate that human milk lactoferrin could be used as a prebiotic chemotherapeutic strategy to limit the impact of bacterial adherence and biofilm formation on GBS-associated disease outcomes., (© 2021 Wiley-VCH GmbH.)

Recent discovery of superconductivity in Nd 0.8 Sr 0.2 NiO 2 motivates the synthesis of other nickelates for providing insights into the origin of high-temperature superconductivity. However, the synthesis of stoichiometric R 1- x Sr x NiO 3 thin films over a range of x has proven challenging. Moreover, little is known about the structures and properties of the end member SrNiO 3 Here, we show that spontaneous phase segregation occurs while depositing SrNiO 3 thin films on perovskite oxide substrates by molecular beam epitaxy. Two coexisting oxygen-deficient Ruddlesden-Popper phases, Sr 2 NiO 3 and SrNi 2 O 3 , are formed to balance the stoichiometry and stabilize the energetically preferred Ni 2+ cation. Our study sheds light on an unusual oxide thin-film nucleation process driven by the instability in perovskite structured SrNiO 3 and the tendency of transition metal cations to form their most stable valence (i.e., Ni 2+ in this case). The resulting metastable reduced Ruddlesden-Popper structures offer a testbed for further studying emerging phenomena in nickel-based oxides., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

Background: Acinetobacter baumannii is a gram-negative bacterium which causes opportunistic infections in immunocompromised hosts. Genome plasticity has given rise to a wide range of strain variation with respect to antimicrobial resistance profiles and expression of virulence factors which lead to altered phenotypes associated with pathogenesis. The purpose of this study was to analyze clinical strains of A. baumannii for phenotypic variation that might correlate with virulence phenotypes, antimicrobial resistance patterns, or strain isolation source. We hypothesized that individual strain virulence phenotypes might be associated with anatomical site of isolation or alterations in susceptibility to antimicrobial interventions., Methodology: A cohort of 17 clinical isolates of A. baumannii isolated from diverse anatomical sites were evaluated to ascertain phenotypic patterns including biofilm formation, hemolysis, motility, and antimicrobial resistance. Antibiotic susceptibility/resistance to ampicillin-sulbactam, amikacin, ceftriaxone, ceftazidime, cefotaxime, ciprofloxacin, cefepime, gentamicin, levofloxacin, meropenem, piperacillin, trimethoprim-sulfamethoxazole, ticarcillin- K clavulanate, tetracyclin, and tobramycin was determined., Results: Antibiotic resistance was prevalent in many strains including resistance to ampicillin-sulbactam, amikacin, ceftriaxone, ceftazidime, cefotaxime, ciprofloxacin, cefepime, gentamicin, levofloxacin, meropenem, piperacillin, trimethoprim-sulfamethoxazole, ticarcillin- K clavulanate, tetracyclin, and tobramycin. All strains tested induced hemolysis on agar plate detection assays. Wound-isolated strains of A. baumannii exhibited higher motility than strains isolated from blood, urine or Foley catheter, or sputum/bronchial wash. A. baumannii strains isolated from patient blood samples formed significantly more biofilm than isolates from wounds, sputum or bronchial wash samples. An inverse relationship between motility and biofilm formation was observed in the cohort of 17 clinical isolates of A. baumannii tested in this study. Motility was also inversely correlated with induction of hemolysis. An inverse correlation was observed between hemolysis and resistance to ticarcillin-k clavulanate, meropenem, and piperacillin. An inverse correlation was also observed between motility and resistance to ampicillin-sulbactam, ceftriaxone, ceftoxamine, ceftazidime, ciprofloxacin, or levofloxacin., Conclusions: Strain dependent variations in biofilm and motility are associated with anatomical site of isolation. Biofilm and hemolysis production both have an inverse association with motility in the cohort of strains utilized in this study, and motility and hemolysis were inversely correlated with resistance to numerous antibiotics.

The ability to tailor oxide heterointerfaces has led to novel properties in low-dimensional oxide systems. A fundamental understanding of these properties is based on the concept of electronic charge transfer. However, the electronic properties of oxide heterointerfaces crucially depend on their ionic constitution and defect structure: ionic charges contribute to charge transfer and screening at oxide interfaces, triggering a thermodynamic balance of ionic and electronic structures. Quantitative understanding of the electronic and ionic roles regarding charge-transfer phenomena poses a central challenge. Here, the electronic and ionic structure is simultaneously investigated at the prototypical charge-transfer heterointerface, LaAlO 3 /SrTiO 3 . Applying in situ photoemission spectroscopy under oxygen ambient, ionic and electronic charge transfer is deconvoluted in response to the oxygen atmosphere at elevated temperatures. In this way, both the rich and variable chemistry of complex oxides and the associated electronic properties are equally embraced. The interfacial electron gas is depleted through an ionic rearrangement in the strontium cation sublattice when oxygen is applied, resulting in an inverse and reversible balance between cation vacancies and electrons, while the mobility of ionic species is found to be considerably enhanced as compared to the bulk. Triggered by these ionic phenomena, the electronic transport and magnetic signature of the heterointerface are significantly altered., (© 2020 The Authors. Advanced Materials published by Wiley-VCH GmbH.)

Alongside Edward, Lemieux was among the earliest researchers studying negative hyperconjugation (i.e., the anomeric effect) or the preference for gauche conformations about the C1-O5 bond in carbohydrates. Lemieux also studied an esoteric, if not controversial, theory known as the reverse anomeric effect (RAE). This theory is used to rationalize scenarios where predicted anomeric stabilization does not occur. One such example is the Kochetkov amination where reducing end amines exist solely as the β-anomer. Herein, we provide a brief account of Lemieux's contributions to the field of stereoelectronics and apply this knowledge toward the synthesis of β-amino human milk oligosaccharides (βΑ-HMOs). These molecules were evaluated for their ability to inhibit growth and biofilm production in Group B Streptococcus (GBS) and Staphylococcus aureus . While the parent HMOs lacked antimicrobial and antibiofilm activity, their β-amino derivatives significantly inhibited biofilm formation in both species. Field emission gun-scanning single electron microscopy (FEG-SEM) revealed that treatment with β-amino HMOs significantly inhibits bacterial adherence and eliminates the ability of both microbes to form biofilms.

Streptococcus species are common causes of human infection. These Gram-positive, encapsulated bacterial pathogens infect diverse anatomic spaces, leading to infections including skin and soft tissue infection, endocarditis, pneumonia, meningitis, sinusitis, otitis media, chorioamnionitis, sepsis, and even death. Risk for streptococcal infection is highest in low- and middle-income countries where micronutrient deficiency is common. Epidemiological data reveal that vitamin D deficiency is associated with enhanced risk of streptococcal infection and cognate disease outcomes. Additionally, vitamin D improves antibacterial defenses by stimulating innate immune processes such as phagocytosis and enhancing production of reactive oxygen species (oxidative burst) and antimicrobial peptides (including cathelicidin and lactoferrin), which are important for efficient killing of bacteria. This review presents the most recent published work that studies interactions between the micronutrient vitamin D, the host immune system, and pathogenic streptococci as well as comparisons with other relevant infection models.

We report the synthesis and antimicrobial studies of a new series of naphthyl-substituted pyrazole-derived hydrazones. Many of these novel compounds are potent growth inhibitors of several strains of drug-resistant bacteria. These potent compounds have inclined growth inhibitory properties for planktonic Staphylococcus aureus and Acinetobacter baumannii, and its drug-resistant variants with minimum inhibitory concentration (MIC) as low as 0.78 and 1.56 µg ml -1 , respectively. These compounds also show potent activity against S. aureus and A. baumannii biofilm formation and eradication properties. Time Kill Assay shows that these compounds are bactericidal for S. aureus and bacteriostatic for A. baumannii. The probable mode of action is the disruption of the bacterial cell membrane. Furthermore, potent compounds are nontoxic to human cell lines at several fold higher concentrations than the MICs.

Creating new functionality in materials containing transition metals is predicated on the ability to control the associated charge states. For a given transition metal, there is an upper limit on valence that is not exceeded under normal conditions. Here, it is demonstrated that this limit of 3+ for Ni and Fe can be exceeded via synthesis of (SrNiO 3 ) m /(LaFeO 3 ) n superlattices by tuning n and m. The Goldschmidt tolerance constraints are lifted, and SrNi 4+ O 3 with holes on adjacent O anions is stabilized as a perovskite at the single-unit-cell level (m = 1). Holding m = 1, spectroscopy reveals that the n = 1 superlattice contains Ni 3+ and Fe 4+ , whereas Ni 4+ and Fe 3+ are observed in the n = 5 superlattice. It is revealed that the B-site cation valences can be tuned by controlling the magnitude of the FeO 6 octahedral rotations, which, in turn, determine the energy balance between Ni 3+ /Fe 4+ and Ni 4+ /Fe 3+ , thus controlling emergent electrical properties such as the band alignment and resulting hole confinement. This approach can be extended to other systems for synthesizing novel, metastable layered structures with new functionalities., (© 2020 Wiley-VCH GmbH.)

Ellagic acid derivatives possess antimicrobial and antibiofilm properties across a wide-range of microbial pathogens. Due to their poor solubility and ambident reactivity it is challenging to synthesize, purify, and characterize the activity of ellagic acid glycosides. In this study, we have synthesized three ellagic acid glycoconjugates and evaluated their antimicrobial and antibiofilm activity in Streptococcus agalactiae (Group B Streptococcus, GBS). Their significant impacts on biofilm formation were examined via SEM to reveal early-stage inhibition of cellular adhesion. Additionally, the synthetic glycosides were evaluated against five of the six ESKAPE pathogens and two fungal pathogens. These studies reveal that the ellagic acid glycosides possess inhibitory effects on the growth of gram-negative pathogens., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Internal electric fields that underpin functioning of multi-component materials systems and devices are coupled to structural and compositional inhomogeneities associated with interfaces in these systems. Hard-x-ray photoelectron spectroscopy is a valuable source of information on band-edge profiles, governed by the distribution of internal fields, deep inside semiconductor thin films and heterojunctions. However, extracting this information requires robust and physically meaningful decomposition of spectra into contributions from individual atomic planes. We present an approach that utilizes the physical requirements of a monotonic dependence of the built-in electrostatic potential on depth and continuity of the potential function and its derivatives. These constraints enable efficient extraction of band-edge profiles and allow one to capture details of the electronic structure, including determination of the signs and magnitudes of the band bending as well as the valence band offsets. The utility of this approach to generate quantitative insight into the electronic structure of complex materials is illustrated for epitaxial [Formula: see text] on intrinsic Si(001).

Oligosaccharides have valuable effects in biological systems, but their complex nature makes them difficult to convert into chemical tools. We have developed a two-step conversion of unprotected oligosaccharides that is highly amenable to generating a variety of complex oligosaccharide tool compounds. This sequence features an optimized Kochetkov amination procedure and subsequent amide coupling. With these simple synthetic conversions, the creation of novel bioorthogonal carbohydrate probes becomes easily accessible and new avenues for chemical biology may be opened.•Optimized Kochetkov amination procedure for complex oligosaccharides.•Highly versatile amide coupling for facile probe synthesis., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 Published by Elsevier B.V.)

Streptococcal species are Gram-positive bacteria responsible for a variety of disease outcomes including pneumonia, meningitis, endocarditis, erysipelas, necrotizing fasciitis, periodontitis, skin and soft tissue infections, chorioamnionitis, premature rupture of membranes, preterm birth, and neonatal sepsis. In response to streptococcal infections, the host innate immune system deploys a repertoire of antimicrobial and immune modulating molecules. One important molecule that is produced in response to streptococcal infections is lactoferrin. Lactoferrin has antimicrobial properties including the ability to bind iron with high affinity and sequester this important nutrient from an invading pathogen. Additionally, lactoferrin has the capacity to alter the host inflammatory response and contribute to disease outcome. This Review presents the most recent published work that studies the interaction between the host innate immune protein lactoferrin and the invading pathogen, Streptococcus .

Starting shortly after parturition, and continuing throughout our lifetime, the gut microbiota coevolves with our metabolic and neurological programming. This symbiosis is regulated by a complex interplay between the host and environmental factors, including diet and lifestyle. Not surprisingly, the development of this microbial community is of critical importance to health and wellness. In this targeted review, we examine the gut microbiome from birth to 2 years of age to characterize the role human milk oligosaccharides play in early formation of microbial flora., (© 2020 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)