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U.S. Toddlers Eat More French Fries Than Vegetables

Title: U.S. Toddlers Eat More French Fries Than Vegetables
Category: Health News
Created: 5/1/2017 12:00:00 AM
Last Editorial Review: 5/1/2017 12:00:00 AM




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Healthy Heart in Middle Age Delivers Big Dividends

Title: Healthy Heart in Middle Age Delivers Big Dividends
Category: Health News
Created: 5/1/2017 12:00:00 AM
Last Editorial Review: 5/2/2017 12:00:00 AM




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Heart Failure, Job Loss May Be Deadly Combo

Title: Heart Failure, Job Loss May Be Deadly Combo
Category: Health News
Created: 5/2/2017 12:00:00 AM
Last Editorial Review: 5/3/2017 12:00:00 AM




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A Toddler's Screen Time Tied to Speech Delay

Title: A Toddler's Screen Time Tied to Speech Delay
Category: Health News
Created: 5/4/2017 12:00:00 AM
Last Editorial Review: 5/4/2017 12:00:00 AM




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Caterpillar Invasion in London Puts People at Risk of Deadly Allergic Reactions

Title: Caterpillar Invasion in London Puts People at Risk of Deadly Allergic Reactions
Category: Health News
Created: 4/30/2018 12:00:00 AM
Last Editorial Review: 5/1/2018 12:00:00 AM




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Simple Drug Packaging Change Could Save Toddlers' Lives

Title: Simple Drug Packaging Change Could Save Toddlers' Lives
Category: Health News
Created: 5/3/2018 12:00:00 AM
Last Editorial Review: 5/3/2018 12:00:00 AM




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Work Stress, Poor Sleep, High Blood Pressure a Deadly Trio

Title: Work Stress, Poor Sleep, High Blood Pressure a Deadly Trio
Category: Health News
Created: 4/29/2019 12:00:00 AM
Last Editorial Review: 4/29/2019 12:00:00 AM




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Nanotechnology Might Help Fight Deadly 'Cytokine Storm' of COVID-19

Title: Nanotechnology Might Help Fight Deadly 'Cytokine Storm' of COVID-19
Category: Health News
Created: 4/28/2020 12:00:00 AM
Last Editorial Review: 4/29/2020 12:00:00 AM




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Middle Age More Stressful Now Than in 1990s: Study

Before the COVID-19 pandemic upended people's lives, Americans were already feeling more stressed than they did a generation ago. Now, new research finds that no group is feeling the impact of additional stress more than middle-aged people.




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HDL vs. LDL Cholesterol (Good and Bad)

Title: HDL vs. LDL Cholesterol (Good and Bad)
Category: Diseases and Conditions
Created: 7/14/2017 12:00:00 AM
Last Editorial Review: 12/11/2019 12:00:00 AM




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Pneumonia More Deadly Than Hip Fractures for Hospitalized Seniors

Title: Pneumonia More Deadly Than Hip Fractures for Hospitalized Seniors
Category: Health News
Created: 4/23/2020 12:00:00 AM
Last Editorial Review: 4/24/2020 12:00:00 AM




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Second HIV Patient Reportedly 'Cured'

Title: Second HIV Patient Reportedly 'Cured'
Category: Health News
Created: 3/9/2020 12:00:00 AM
Last Editorial Review: 3/10/2020 12:00:00 AM




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Middle Age More Stressful Now Than in 1990s: Study

Title: Middle Age More Stressful Now Than in 1990s: Study
Category: Health News
Created: 5/7/2020 12:00:00 AM
Last Editorial Review: 5/8/2020 12:00:00 AM




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Cuddling Brings Two Minds Together, MRI Study Reveals

Title: Cuddling Brings Two Minds Together, MRI Study Reveals
Category: Health News
Created: 5/4/2020 12:00:00 AM
Last Editorial Review: 5/4/2020 12:00:00 AM




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Two previously unrecorded xiphosurid trace fossils, Selenichnites rossendalensis and Crescentichnus tesiltus, from the Middle Jurassic of Yorkshire, UK

The invertebrate trace fossils Selenichnites rossendalensis and Crescentichnus tesiltus are recorded and described from the Middle Jurassic Gristhorpe Member of the Cloughton Formation of the Cleveland Basin. This is the first record of these ichnospecies from the basin and now completes the occurrence of these and other traces assumed to have been made by limulids from all three non-marine formations of the Ravenscar Group.




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Myeloid-specific deficiency of pregnane X receptor decreases atherosclerosis in LDL receptor-deficient mice [Research Articles]

The pregnane X receptor (PXR) is a nuclear receptor that can be activated by numerous drugs and xenobiotic chemicals. PXR thereby functions as a xenobiotic sensor to coordinately regulate host responses to xenobiotics by transcriptionally regulating many genes involved in xenobiotic metabolism. We have previously reported that PXR has pro-atherogenic effects in animal models, but how PXR contributes to atherosclerosis development in different tissues or cell types remains elusive. In this study, we generated an LDL receptor-deficient mouse model with myeloid-specific PXR deficiency (PXRMyeLDLR–/–) to elucidate the role of macrophage PXR signaling in atherogenesis. The myeloid PXR deficiency did not affect metabolic phenotypes and plasma lipid profiles, but PXRMyeLDLR–/– mice had significantly decreased atherosclerosis at both aortic root and brachiocephalic arteries compared with control littermates. Interestingly, the PXR deletion did not affect macrophage adhesion and migration properties, but reduced lipid accumulation and foam cell formation in the macrophages. PXR deficiency also led to decreased expression of the scavenger receptor CD36 and impaired lipid uptake in macrophages of the PXRMyeLDLR–/– mice. Further, RNA-Seq analysis indicated that treatment with a prototypical PXR ligand affects the expression of many atherosclerosis-related genes in macrophages in vitro. These findings reveal a pivotal role of myeloid PXR signaling in atherosclerosis development and suggest that PXR may be a potential therapeutic target in atherosclerosis management.




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A Polar Flagellar Transcriptional Program Mediated by Diverse Two-Component Signal Transduction Systems and Basal Flagellar Proteins Is Broadly Conserved in Polar Flagellates

ABSTRACT

Bacterial flagella are rotating nanomachines required for motility. Flagellar gene expression and protein secretion are coordinated for efficient flagellar biogenesis. Polar flagellates, unlike peritrichous bacteria, commonly order flagellar rod and hook gene transcription as a separate step after production of the MS ring, C ring, and flagellar type III secretion system (fT3SS) core proteins that form a competent fT3SS. Conserved regulatory mechanisms in diverse polar flagellates to create this polar flagellar transcriptional program have not been thoroughly assimilated. Using in silico and genetic analyses and our previous findings in Campylobacter jejuni as a foundation, we observed a large subset of Gram-negative bacteria with the FlhF/FlhG regulatory system for polar flagellation to possess flagellum-associated two-component signal transduction systems (TCSs). We present data supporting a general theme in polar flagellates whereby MS ring, rotor, and fT3SS proteins contribute to a regulatory checkpoint during polar flagellar biogenesis. We demonstrate that Vibrio cholerae and Pseudomonas aeruginosa require the formation of this regulatory checkpoint for the TCSs to directly activate subsequent rod and hook gene transcription, which are hallmarks of the polar flagellar transcriptional program. By reprogramming transcription in V. cholerae to more closely follow the peritrichous flagellar transcriptional program, we discovered a link between the polar flagellar transcription program and the activity of FlhF/FlhG flagellar biogenesis regulators in which the transcriptional program allows polar flagellates to continue to produce flagella for motility when FlhF or FlhG activity may be altered. Our findings integrate flagellar transcriptional and biogenesis regulatory processes involved in polar flagellation in many species.

IMPORTANCE Relative to peritrichous bacteria, polar flagellates possess regulatory systems that order flagellar gene transcription differently and produce flagella in specific numbers only at poles. How transcriptional and flagellar biogenesis regulatory systems are interlinked to promote the correct synthesis of polar flagella in diverse species has largely been unexplored. We found evidence for many Gram-negative polar flagellates encoding two-component signal transduction systems with activity linked to the formation of flagellar type III secretion systems to enable production of flagellar rod and hook proteins at a discrete, subsequent stage during flagellar assembly. This polar flagellar transcriptional program assists, in some manner, the FlhF/FlhG flagellar biogenesis regulatory system, which forms specific flagellation patterns in polar flagellates in maintaining flagellation and motility when activity of FlhF or FlhG might be altered. Our work provides insight into the multiple regulatory processes required for polar flagellation.




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Maternal Broadly Neutralizing Antibodies Can Select for Neutralization-Resistant, Infant-Transmitted/Founder HIV Variants

ABSTRACT

Each year, >180,000 infants become infected via mother-to-child transmission (MTCT) of HIV despite the availability of effective maternal antiretroviral treatments, underlining the need for a maternal HIV vaccine. We characterized 224 maternal HIV envelope (Env)-specific IgG monoclonal antibodies (MAbs) from seven nontransmitting and transmitting HIV-infected U.S. and Malawian mothers and examined their neutralization activities against nontransmitted autologous circulating viruses and infant-transmitted founder (infant-T/F) viruses. Only a small subset of maternal viruses, 3 of 72 (4%), were weakly neutralized by maternal linear V3 epitope-specific IgG MAbs, whereas 6 out of 6 (100%) infant-T/F viruses were neutralization resistant to these V3-specific IgG MAbs. We also show that maternal-plasma broadly neutralizing antibody (bNAb) responses targeting the V3 glycan supersite in a transmitting woman may have selected for an N332 V3 glycan neutralization-resistant infant-T/F virus. These data have important implications for bNAb-eliciting vaccines and passively administered bNAbs in the setting of MTCT.

IMPORTANCE Efforts to eliminate MTCT of HIV with antiretroviral therapy (ART) have met little success, with >180,000 infant infections each year worldwide. It is therefore likely that additional immunologic strategies that can synergize with ART will be required to eliminate MTCT of HIV. To this end, understanding the role of maternal HIV Env-specific IgG antibodies in the setting of MTCT is crucial. In this study, we found that maternal-plasma broadly neutralizing antibody (bNAb) responses can select for T/F viruses that initiate infection in infants. We propose that clinical trials testing the efficacy of single bNAb specificities should not include HIV-infected pregnant women, as a single bNAb might select for neutralization-resistant infant-T/F viruses.




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Towards a Mechanism for Poly(I{middle dot}C) Antiviral Priming in Oysters

ABSTRACT

Viral diseases cause significant losses in aquaculture. Prophylactic measures, such as immune priming, are promising control strategies. Treatment of the Pacific oyster (Crassostrea gigas) with the double-stranded RNA analog poly(I·C) confers long-term protection against infection with ostreid herpesvirus 1, the causative agent of Pacific oyster mortality syndrome. In a recent article in mBio, Lafont and coauthors (M. Lafont, A. Vergnes, J. Vidal-Dupiol, J. de Lorgeril, et al., mBio 11:e02777-19, 2020, https://doi.org/10.1128/mBio.02777-19) characterized the transcriptome of oysters treated with poly(I·C). This immune stimulator induced genes related to the interferon and apoptosis pathways. This response overlaps the response to viral infection, and high expression levels of potential effector genes are maintained for up to 4 months. This work opens the door to characterization of the phenomena of immune priming in a poorly studied invertebrate model. It also highlights the importance of interferon-like responses for invertebrate antiviral immunity.




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Single-Dose, Intranasal Immunization with Recombinant Parainfluenza Virus 5 Expressing Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Spike Protein Protects Mice from Fatal MERS-CoV Infection

ABSTRACT

Middle East respiratory syndrome coronavirus (MERS-CoV) can cause severe and fatal acute respiratory disease in humans and remains endemic in the Middle East since first being identified in 2012. There are currently no approved vaccines or therapies available for MERS-CoV. In this study, we evaluated parainfluenza virus 5 (PIV5)-based vaccine expressing the MERS-CoV envelope spike protein (PIV5/MERS-S) in a human DPP4 knockin C57BL/6 congenic mouse model (hDPP4 KI). Following a single-dose intranasal immunization, PIV5-MERS-S induced neutralizing antibody and robust T cell responses in hDPP4 KI mice. A single intranasal administration of 104 PFU PIV5-MERS-S provided complete protection against a lethal challenge with mouse-adapted MERS-CoV (MERSMA6.1.2) and improved virus clearance in the lung. In comparison, single-dose intramuscular immunization with 106 PFU UV-inactivated MERSMA6.1.2 mixed with Imject alum provided protection to only 25% of immunized mice. Intriguingly, an influx of eosinophils was observed only in the lungs of mice immunized with inactivated MERS-CoV, suggestive of a hypersensitivity-type response. Overall, our study indicated that PIV5-MERS-S is a promising effective vaccine candidate against MERS-CoV infection.

IMPORTANCE MERS-CoV causes lethal infection in humans, and there is no vaccine. Our work demonstrates that PIV5 is a promising vector for developing a MERS vaccine. Furthermore, success of PIV5-based MERS vaccine can be employed to develop a vaccine for emerging CoVs such as SARS-CoV-2, which causes COVID-19.




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Conductance Mechanisms of Rapidly Desensitizing Cation Channelrhodopsins from Cryptophyte Algae

ABSTRACT

Channelrhodopsins guide algal phototaxis and are widely used as optogenetic probes for control of membrane potential with light. "Bacteriorhodopsin-like" cation channelrhodopsins (BCCRs) from cryptophytes differ in primary structure from other CCRs, lacking usual residues important for their cation conductance. Instead, the sequences of BCCR match more closely those of rhodopsin proton pumps, containing residues responsible for critical proton transfer reactions. We report 19 new BCCRs which, together with the earlier 6 known members of this family, form three branches (subfamilies) of a phylogenetic tree. Here, we show that the conductance mechanisms in two subfamilies differ with respect to involvement of the homolog of the proton donor in rhodopsin pumps. Two BCCRs from the genus Rhodomonas generate photocurrents that rapidly desensitize under continuous illumination. Using a combination of patch clamp electrophysiology, absorption, Raman spectroscopy, and flash photolysis, we found that the desensitization is due to rapid accumulation of a long-lived nonconducting intermediate of the photocycle with unusually blue-shifted absorption with a maximum at 330 nm. These observations reveal diversity within the BCCR family and contribute to deeper understanding of their independently evolved cation channel function.

IMPORTANCE Cation channelrhodopsins, light-gated channels from flagellate green algae, are extensively used as optogenetic photoactivators of neurons in research and recently have progressed to clinical trials for vision restoration. However, the molecular mechanisms of their photoactivation remain poorly understood. We recently identified cryptophyte cation channelrhodopsins, structurally different from those of green algae, which have separately evolved to converge on light-gated cation conductance. This study reveals diversity within this new protein family and describes a subclade with unusually rapid desensitization that results in short transient photocurrents in continuous light. Such transient currents have not been observed in the green algae channelrhodopsins and are potentially useful in optogenetic protocols. Kinetic UV-visible (UV-vis) spectroscopy and photoelectrophysiology reveal that the desensitization is caused by rapid accumulation of a nonconductive photointermediate in the photochemical reaction cycle. The absorption maximum of the intermediate is 330 nm, the shortest wavelength reported in any rhodopsin, indicating a novel chromophore structure.




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A new cheiracanthid acanthodian from the Middle Devonian (Givetian) Orcadian Basin of Scotland and its biostratigraphic and biogeographical significance

A number of partial articulated specimens of Cheiracanthus peachi nov. sp. have been collected from the Mey Flagstone Formation and Rousay Flagstone Formation within the Orcadian Basin of northern Scotland. The new, robust-bodied species is mainly distinguished by the scale ornament of radiating grooves rather than ridges. Compared to other Cheiracanthus species in the Orcadian Basin, C. peachi nov. sp. has quite a short range making it a useful zone fossil. As well as describing the general morphology of the specimens, we have also described and figured SEM images of scales and histological sections of all elements, enabling identification of other, isolated remains. Of particular biological interest is the identification of relatively robust, tooth-like gill rakers. Finally, the species has also been identified from isolated scales in Belarus, where it appears earlier and has a longer stratigraphical range, implying the species evolved in the marine deposits of the east and migrated west into the Orcadian Basin via the river systems.




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Low-carbon GeoEnergy resource options in the Midland Valley of Scotland, UK

Scotland is committed to be a carbon-neutral society by 2040 and has achieved the important initial step of decarbonizing power production. However, more ambitious measures are required to fully decarbonize all of the electricity, transport and heating sectors.

We explore the potential to use low-carbon GeoEnergy resources and bioenergy combined with Carbon Capture and Storage (BECCS) in the Midland Valley area to decarbonize the Scottish economy and society. The Midland Valley has a long history of geological resource extraction and, as a result, the geology of the region is well characterized.

Geothermal energy and subsurface energy storage have the potential to be implemented. Some of them, such as gravity and heat storage, could re-use the redundant mining infrastructure to decrease investment costs. Hydrogen storage could be of particular interest as the Midland Valley offers the required caprock–reservoir assemblages. BECCS is also a promising option to reduce overall CO2 emissions by between 1.10 and 4.40 MtCO2 a–1. The Midland Valley has enough space to grow the necessary crops, but CO2 storage will most likely be implemented in North Sea saline aquifers. The studied aspects suggest that the Midland Valley represents a viable option in Scotland for the exploitation of the majority of low-carbon GeoEnergy resources.

Thematic collection: This article is part of the ‘Early Career Research’ available at: https://www.lyellcollection.org/cc/SJG-early-career-research




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Development of the Proximal-Anterior Skeletal Elements in the Mouse Hindlimb Is Regulated by a Transcriptional and Signaling Network Controlled by Sall4 [Developmental and Behavioral Genetics]

The vertebrate limb serves as an experimental paradigm to study mechanisms that regulate development of the stereotypical skeletal elements. In this study, we simultaneously inactivated Sall4 using Hoxb6Cre and Plzf in mouse embryos, and found that their combined function regulates development of the proximal-anterior skeletal elements in hindlimbs. The Sall4; Plzf double knockout exhibits severe defects in the femur, tibia, and anterior digits, distinct defects compared to other allelic series of Sall4; Plzf. We found that Sall4 regulates Plzf expression prior to hindlimb outgrowth. Further expression analysis indicated that Hox10 genes and GLI3 are severely downregulated in the Sall4; Plzf double knockout hindlimb bud. In contrast, PLZF expression is reduced but detectable in Sall4; Gli3 double knockout limb buds, and SALL4 is expressed in the Plzf; Gli3 double knockout limb buds. These results indicate that Plzf, Gli3, and Hox10 genes downstream of Sall4, regulate femur and tibia development. In the autopod, we show that Sall4 negatively regulates Hedgehog signaling, which allows for development of the most anterior digit. Collectively, our study illustrates genetic systems that regulate development of the proximal-anterior skeletal elements in hindlimbs.




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Oxygen supply capacity in animals evolves to meet maximum demand at the current oxygen partial pressure regardless of size or temperature [RESEARCH ARTICLE]

Brad A. Seibel and Curtis Deutsch

The capacity to extract oxygen from the environment and transport it to respiring tissues in support of metabolic demand reportedly has implications for species’ thermal tolerance, body-size, diversity and biogeography. Here we derive a quantifiable linkage between maximum and basal metabolic rate and their oxygen, temperature and size dependencies. We show that, regardless of size or temperature, the physiological capacity for oxygen supply precisely matches the maximum evolved demand at the highest persistently available oxygen pressure and this is the critical PO2 for the maximum metabolic rate. For most terrestrial and shallow-living marine species, this "Pcrit-max" is the current atmospheric pressure, 21 kPa. Any reduction in oxygen partial pressure from current values will result in a calculable decrement in maximum metabolic performance. However, oxygen supply capacity has evolved to match demand across temperatures and body sizes and so does not constrain thermal tolerance or cause the well-known reduction in mass-specific metabolic rate with increasing body mass. The critical oxygen pressure for resting metabolic rate, typically viewed as an indicator of hypoxia tolerance, is, instead, simply a rate-specific reflection of the oxygen supply capacity. A compensatory reduction in maintenance metabolic costs in warm-adapted species constrains factorial aerobic scope and the critical PO2 to a similar range, between ~2 and 6, across each species’ natural temperature range. The simple new relationship described here redefines many important physiological concepts and alters their ecological interpretation.




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Sedimentary and diapiric melanges in the Skrzydlna area (Outer Carpathians of Poland) as indicators of basinal and structural evolution

The Dukla Nappe in the Skrzydlna area exposes two types of mélange reflecting two different phases of basinal and tectonic evolution of the Outer West Carpathian orogen in its Polish sector. The Oligocene-age sedimentary mélange (olistostrome) is related to growth of the accretionary wedge, whereas the Miocene-age diapiric mélange postdates the orogenic thrusting. Textural and structural features of the very coarse-grained sedimentary mélange suggest non-cohesive debris flows and high-density turbidity currents as predominant emplacement mechanisms. Growth strata, associated with progressive unconformities, and facies contrast between the underlying fine-grained unit and the overlying olistostrome reflect a considerable uplift of the source area and rotation of the adjacent part of the basin floor. The olistostrome and the overlying turbidite succession form a retrogressive sequence interpreted as a submarine canyon infill grading to a small submarine fan. The diapiric mélange, injected into the Oligocene-age succession of the Dukla Nappe, contains the Early and Late Cretaceous-age blocks and matrix derived from the underlying Silesian Nappe. The features reflecting diapiric emplacement include matrix proportion increase and block content decrease towards the mélange margins, scaly fabric and shear zones. Both mélanges, interpreted in the past as chaotic bodies, upon detailed examination reveal genesis-related subtle internal organization.




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High-resolution carbon isotope stratigraphy of the Lower and Middle Ordovician succession of the Yangtze Platform, China: implications for global correlation

The Lower and Middle Ordovician of the Yangtze Platform, China, is characterized by a sedimentary succession dominated by carbonate rocks. Three sections spanning the Nantsinkuan/Lunshan, Fenhsiang, Hunghuayuan, and Dawan/Zitai formations, corresponding to the Tremadocian–Dapingian in age, have been sampled for high-resolution 13C chemostratigraphy (542 samples in total). Our new 13C data reveal five tie-points with the potential for global correlation: (1) a positive 13C excursion in the lower Nantsinkuan Formation within the Tremadocian Rossodus manitouensis Zone; (2) an excursion with two peaks roughly within the late Tremadocian Paltodusdeltifer’ Zone; (3) a positive 13C shift in the lower Hunghuayuan Formation, within the early Floian Serratognathus diversus Zone; (4) a gradual positive 13C shift in the late Floian, ranging from the uppermost S. diversus Zone to the basal Oepikodus evae Zone; (5) a minor negative shift in the lower Dawan/Zitai Formation, within the early Dapingian Baltoniodus triangularis Zone. These excursions are herein used for correlation of the Yangtze Platform strata with successions from South China, North China, the Argentine Precordillera, North America and Baltica. From a palaeogeographical perspective the Gudongkou, Xiangshuidong and Daling sections represent depositional environments along an inner to outer ramp profile. 13C data from these sections show successively heavier (higher) 13C values with increasing depositional depth. This is interpreted as due to remineralization of organic carbon within the carbonate rocks.

Supplementary material: Carbon and oxygen isotope data are available at: https://doi.org/10.6084/m9.figshare.c.4767080




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Correction to "Probing the Assembly of HDL Mimetic, Drug Carrying Nanoparticles Using Intrinsic Fluorescence" [Erratum]




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An aberrant bi-apical Follicucullus (Albaillellaria) from the late Guadalupian (Middle Permian), with the possible oldest evidence of double malformation in radiolarians

An aberrant bi-apical Follicucullus specimen (Albaillellaria, Radiolaria) has been discovered from an upper Guadalupian (Middle Permian) chert block of the Kamiaso Unit of the Mino terrane, central Japan. If this specimen was formed with double malformation, it would be the oldest record of this phenomenon in radiolarians and the first record of its kind in Albaillellaria.




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DLL1- and DLL4-Mediated Notch Signaling Is Essential for Adult Pancreatic Islet Homeostasis

Genes of the Notch signaling pathway are expressed in different cell types and organs at different time points during embryonic development and adulthood. The Notch ligand Delta-like 1 (DLL1) controls the decision between endocrine and exocrine fates of multipotent progenitors in the developing pancreas, and loss of Dll1 leads to premature endocrine differentiation. However, the role of Delta-Notch signaling in adult tissue homeostasis is not well understood. Here, we describe the spatial expression pattern of Notch pathway components in adult murine pancreatic islets and show that DLL1 and DLL4 are specifically expressed in β-cells, whereas JAGGED1 is expressed in α-cells. We show that mice lacking both DLL1 and DLL4 in adult β-cells display improved glucose tolerance, increased glucose-stimulated insulin secretion, and hyperglucagonemia. In contrast, overexpression of the intracellular domain of DLL1 in adult murine pancreatic β-cells results in impaired glucose tolerance and reduced insulin secretion, both in vitro and in vivo. These results suggest that Notch ligands play specific roles in the adult pancreas and highlight a novel function of the Delta/Notch pathway in β-cell insulin secretion.




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Apolipoprotein M and Sphingosine-1-Phosphate: A Potentially Antidiabetic Tandem Carried by HDL




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Lactoferrin Is Broadly Active against Yeasts and Highly Synergistic with Amphotericin B [Susceptibility]

Lactoferrin (LF) is a multifunctional milk protein with antimicrobial activity against a range of pathogens. While numerous studies report that LF is active against fungi, there are considerable differences in the level of antifungal activity and the capacity of LF to interact with other drugs. Here we undertook a comprehensive evaluation of the antifungal spectrum of activity of three defined sources of LF across 22 yeast and 24 mold species and assessed its interactions with six widely used antifungal drugs. LF was broadly and consistently active against all yeast species tested (MICs, 8 to 64 μg/ml), with the extent of activity being strongly affected by iron saturation. LF was synergistic with amphotericin B (AMB) against 19 out of 22 yeast species tested, and synergy was unaffected by iron saturation but was affected by the extent of LF digestion. LF-AMB combination therapy significantly prolonged the survival of Galleria mellonella wax moth larvae infected with Candida albicans or Cryptococcus neoformans and decreased the fungal burden 12- to 25-fold. Evidence that LF directly interacts with the fungal cell surface was seen via scanning electron microscopy, which showed pore formation, hyphal thinning, and major cell collapse in response to LF-AMB synergy. Important virulence mechanisms were disrupted by LF-AMB treatment, which significantly prevented biofilms in C. albicans and C. glabrata, inhibited hyphal development in C. albicans, and reduced cell and capsule size and phenotypic diversity in Cryptococcus. Our results demonstrate the potential of LF-AMB as an antifungal treatment that is broadly synergistic against important yeast pathogens, with the synergy being attributed to the presence of one or more LF peptides.




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Thalamic Massa Intermedia in Children with and without Midline Brain Malformations [PEDIATRICS]

BACKGROUND AND PURPOSE:

The massa intermedia is a normal midline transventricular thalamic connection. Massa intermedia aberrations are common in schizophrenia, Chiari II malformation, X-linked hydrocephalus, Cornelia de Lange syndrome, and diencephalic-mesencephalic junction dysplasia, among others. We have noticed that massa intermedia abnormalities often accompany other midline malformations. The massa intermedia has never been formally evaluated in a group of exclusively pediatric patients, to our knowledge. We sought to compare and contrast the prevalence, size, and location of the massa intermedia in pediatric patients with and without congenital midline brain abnormalities.

MATERIALS AND METHODS:

Successive 3T brain MR imaging examinations from pediatric patients with and without midline malformations were procured from the imaging data base at a pediatric hospital. Massa intermedia presence, size, morphology, and position were determined using 3D-TIWI with 1-mm isotropic resolution. The brain commissures, septum pellucidum, hypothalamus, hippocampus, vermis, and brain stem were evaluated to determine whether alterations were related to or predictive of massa intermedia abnormalities.

RESULTS:

The massa intermedia was more frequently absent, dysmorphic, and/or displaced in patients with additional midline abnormalities than in those without. The massa intermedia was absent in 40% of patients with midline malformations versus 12% of patients with normal findings (P < .001). Massa intermedia absence, surface area, and morphology were predictable by various attributes and alterations of the commissures, hippocampus, hypothalamus, vermis, brain stem, and third ventricle.

CONCLUSIONS:

Most pediatric patients have a thalamic massa intermedia centered in the anterior/superior third ventricle. Massa intermedia abnormalities are commonly associated with other midline malformations. Normal-variant massa intermedia absence is a diagnosis of exclusion.




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Chung cư DLC Complex

Chung cư DLC Complex là tổ hợp trung tâm thương mại và căn hộ chung cư tọa lạc ngay ngã tư Nguyễn Tuân giao với Ngụy Như Kon Tum, một trong những vị trí đắc địa tại khu đô thị Trung Hòa Nhân Chính cũng như quận Thanh Xuân, Hà Nội.




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Legal advice for landlords who rent houses to foreigners

By cause of the rising number of expats in Vietnam, the lease market for foreigners has significantly expanded in recent years. However, foreign tenants and their landlords should consider the following legal advice to avoid unwanted risk.




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Tips for landlords to minimize risk

Leasing houses has been an attractive investment in big cities as it makes a stable income out of existing assets. However, to minimize the potential risks, landlords should pay attention to the following tips.




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Cho thuê nhà KDL Bình Quới 2, Bình Thạnh, Hồ Chí Minh, nhà mới giá rẻ LH 0987413594

Cho thuê nhà KDL Bình Quới 2, phường 28, quận Bình Thạnh, Hồ Chí Minh. Nhà mới xây, 1 trệt và 1 lầu, 2 phòng ngủ, 1 bếp, 1 phòng khách, 1 toilet, 1 sân đậu xe hơi. Hẻm xe tải. Không gian yên tỉnh, gần sông. Giá: 6,5 triệu/tháng. Liên hệ: Bà Sáu, 0987413594 (Miễn tiếp trung gian, ...




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Goldlink - Văn phòng cho thuê Cityland, full nội thất, giá chỉ từ 6tr/th, LH: 0979.30.28.28

Goldlink chuyên cho thuê mua bán nhà Cityland Gò Vấp.* Cho thuê văn phòng tại khu dân cư Cityland Park Hills Gò Vấp. * Nằm ngay trung tâm Gò Vấp, cách sân bay chỉ 5' đi xe, thuận tiện di chuyển đến các quận lân cận. * Vị trí căn góc, tiện kinh doanh, Mặt tiền đường lớn ô tô đậu t...




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Landlord/Tenant Relationship

The relationship between a landlord and his tenant is often fraught with tension. Just ask the average unhappy tenant and he will most likely tell you that his landlord’s sole ambition is to rip him off and make his life as difficult as possible. An unhappy landlord on the other hand, tends to view the situation somewhat differently and feels that no matter how much he does for his tenant, there are always problems, and always reasons to delay paying the rent.




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Vampire: The Masquerade - Bloodlines 2 Confirmed for Xbox Series X

It was confirmed at the Inside Xbox event today Vampire: The Masquerade - Bloodlines 2 will be getting a next generation release on the Xbox Series X. It was already confirmed the game will release on the PlayStation 4, Xbox One and Windows PC.

View the latest trailer below:

Here is an overview of the game:

Enter the World of Darkness and rise through vampire society. Experience Seattle - a city full of alluring, dangerous, characters and factions. You are dead now but stronger, quicker, more alluring and with potential for so much more. Choose to be brutal and unflinching or cultured and seductive. Use charm, cunning, terror and sheer will to rise through vampire society. What monster will you be?

A life-long and avid gamer, William D'Angelo was first introduced to VGChartz in 2007. After years of supporting the site, he was brought on in 2010 as a junior analyst, working his way up to lead analyst in 2012. He has expanded his involvement in the gaming community by producing content on his own YouTube channel and Twitch channel dedicated to gaming Let's Plays and tutorials. You can contact the author at wdangelo@vgchartz.com or on Twitter @TrunksWD.

Full Article - https://www.vgchartz.com/article/443424/vampire-the-masquerade-bloodlines-2-confirmed-for-xbox-series-x/




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