Outer membrane protein A (OmpA) deficient Salmonella Typhimurium displays enhanced susceptibility towards β-lactam antibiotics: third-generation cephalosporins (ceftazidime) and carbapenems (meropenem)

The invasive non-typhoidal serovar of Salmonella enterica, namely Salmonella Typhimurium ST313, causes bloodstream infection in sub-Saharan Africa. Like other bacterial pathogens, the development of antimicrobial resistance is a severe problem in curing non-typhoidal Salmonella infection. In this work, we have investigated the role of four prominent outer membrane porins of S. Typhimurium, namely OmpA, OmpC, OmpD, and OmpF, in resistance against broad-spectrum β-lactam antibiotics- ceftazidime and meropenem. We found that deleting OmpA from Salmonella makes the bacteria susceptible to β-lactam drugs. The MIC for both the antibiotics reduced significantly for STM ΔompA compared to the wild-type and the ompA complemented strains. Despite the presence of antibiotics, the uninterrupted growth of STM ΔompC, ΔompD, and ΔompF endorsed the dispensability of these three porins in antimicrobial resistance. The β-lactam antibiotics caused massive depolarization in the outer membrane of the bacteria in the absence of OmpA. We have proved that none of the extracellular loops but the complete structure of perfectly folded OmpA is required by the bacteria for developing antimicrobial resistance. Our data revealed that STM ΔompA consumed more antibiotics than the wild-type and the complemented strain, resulting in severe damage of the bacterial outer membrane and subsequent killing of the pathogen by antibiotic-mediated oxidative stress. Upon deleting ompA, the steady decrease in the relative proportion of antibiotic-resistant persisters and the clearance of the STM ΔompA from the liver and spleen of C57BL/6 mice upon treatment with ceftazidime proved the role of OmpA in rendering protection against β-lactam antibiotics.

Study of a Waste Kaolin as Raw Material for Mullite Ceramics and Mullite Refractories by Reaction Sintering

A deposit of raw kaolin, located in West Andalusia (Spain), was studied in this work using a representative sample. The methods of characterization were X-ray diffraction (XRD), X-ray fluorescence (XRF), particle size analysis by sieving and sedimentation, and thermal analysis. The ceramic properties were determined. A sample of commercial kaolin from Burela (Lugo, Spain), with applications in the ceramic industry, was used in some determinations for comparison purposes. The kaolin deposit has been produced by alteration of feldspar-rich rocks. This raw kaolin was applied as an additive in local manufactures of ceramics and refractories. However, there is not previous studies concerning its characteristics and firing properties. Thus, the meaning of this investigation was to conduct a scientific study on this subject and to evaluate the possibilities of application. The raw kaolin was washed for the beneficiation of the rock using water to increase the kaolinite content of the resultant material. The results indicated that the kaolinite content of the raw material was 20 wt % as determined by XRD, showing ~23 wt % of particles lower than 63 µm. The kaolinite content of the fraction lower than 63 µm was 50 wt %. Thus, an improvement of the kaolinite content of this raw kaolin was produced by wet separation. However, the kaolin was considered as a waste kaolin, with microcline, muscovite and quartz identified by XRD. Thermal analyses by Thermo-Dilatometry (TD), Differential Thermal Analysis (DTA) and Thermo-Gravimetry (TG) allowed observe kaolinite thermal decomposition, quartz phase transition and sintering effects. Pressed samples of this raw kaolin, the fraction lower than 63 µm obtained by water washing and the raw kaolin ground using a hammer mill were fired at several temperatures in the range 1000–1500 °C for 2 h. The ceramic properties of all these samples were determined and compared. The results showed the progressive linear firing shrinkage by sintering in these samples, with a maximum value of ~9% in the fraction lower than 63 µm. In general, water absorption capacity of the fired samples showed a decrease from ~18–20% at 1050 °C up to almost zero after firing at 1300 °C, followed by an increase of the experimental values. The open porosity was almost zero after firing at 1350 °C for 2 h and the bulk density reached a maximum value of 2.40 g/cm3 as observed in the ground raw kaolin sample. The XRD examination of fired samples indicated that they are composed by mullite, from kaolinite thermal decomposition, and quartz, present in the raw sample, as main crystalline phases besides a vitreous phase. Fully-densified or vitrified materials were obtained by firing at 1300–1350 °C for 2 h. In a second step of this research, it was examined the promising application of the previous study to increase the amount of mullite by incorporation of alumina (α-alumina) to this kaolin sample. Firing of mixtures, prepared using this kaolin and α-alumina under wet processing conditions, produced the increase of mullite in relative proportion by reaction sintering at temperatures higher than 1500 °C for 2 h. Consequently, a mullite refractory can be prepared using this kaolin. This processing of high-alumina refractories is favoured by a previous size separation, which increases the kaolinite content, or better a grinding treatment of the raw kaolin.

Role of Yap1 in adult neural stem cell activation

Most adult hippocampal neural stem cells (NSCs) remain quiescent with only a minor portion undergoing active proliferation and neurogenesis. The molecular mechanisms that trigger eventually the transition from quiescence to activation are still poorly understood. Here, we found the activity of the transcriptional activator Yap1 to be enriched in active NSCs. Genetic deletion of Yap1 led to a significant reduction in the relative proportion of active NSCs supporting a physiological role of Yap1 in regulating the transition from quiescence to activation. Overexpression of wild type Yap1 in adult NSCs did not induce NSC activation suggesting tight upstream control mechanisms, but overexpression of a gain-of-function mutant (Yap1-5SA) elicited cell cycle entry in NSCs and hilar astrocytes. Consistent with a role of Yap1 in NSC activation, single cell RNA sequencing revealed the partial induction of an activated NSC gene expression program. Yet, Yap1-5SA expression also induced Taz and other key components of the Yap/Taz regulon previously identified in glioblastoma stem cell-like cells. Consequently, dysregulated Yap1 activity led to repression of hippocampal neurogenesis, promoting aberrant differentiation instead.

Silviculture can facilitate repeat prescribed burn programs with long-term strategies

A significant expansion of prescribed fire activity will be necessary to mitigate growing wildfire hazard in California forests. Forest managers can facilitate this expansion by promoting forest structures that allow for more effective implementation of prescribed fire, for both initial-entry and repeat burns. We analyzed changes in surface fuel during a series of three burns in replicated mixed-conifer stands following a period of over 100 years of fire suppression and exclusion. Total fuel load, proportion of pine present, canopy cover and basal area of live trees were relevant forest-structure components that influenced plot-scale fuel consumption. The study highlighted the importance of pre-fire fuel load and the relative proportion of pine in the overstory, which both led to greater amounts of fuel consumption. The initial-entry burn dramatically reduced all fuel categories (fine fuel, coarse wood and duff). Following each burn, fuel recovered until the next burn reduced loads enough to maintain low fuel levels. We apply the results to provide an example of how to determine the timing of prescribed fires.

Phase transformation of the corrosion layers on nuclear fuel cladding. Raman spectroscopy study.

The goal of this work was the phase analysis of corrosion layers on zirconium alloys. In the environment of nuclear reactors, zirconium alloys are covered with a protective layer of zirconium oxide, which occurs in two crystalline modifications - monoclinic and tetragonal. The distribution of these phases in the corrosion layer can affect the overall corrosion rate. Raman spectroscopy was used to determine the composition of the corrosion layers. The use of this method is advantageous because the monoclinic and tetragonal phases can be easily distinguished in the spectra of the corrosion layers. In total, samples of two alloys were measured. The samples were pre-exposed at 360 °C in Li+ containing water (70 mg/l Li as LiOH) . Exposure times were between 21 d and 231 d, so the series contained both pre- and post- transition samples. The relative proportion of the tetragonal phase decreases significantly after the transient. It has also been found that the corrosion layers are highly heterogeneous in terms of the distribution of crystalline modifications.

Inhibitory Effect and Potential Mechanism of Lactobacillus plantarum YE4 against Dipeptidyl Peptidase-4

This study investigated the inhibitory effect and mechanism of 12 LAB strains isolated from Chinese fermented foods on dipeptidyl peptidase-4 (DPP-4) using the Caco-2 cell model. The results showed that the inhibitory effect of cell-free extracts (CFEs) collected from each LAB strain on DPP-4 was higher than that of the cell-free excretory supernatants. The CFEs from Lactobacillus plantarum YE4 (YE4-CFE) exhibited the strongest DPP-4 inhibitory activity (24.33% inhibition). Furthermore, YE4-CFE altered the TNF and MAPK signaling pathways. Additionally, the YE4-CFE ultrafiltration fraction (<3 kDa) displayed a similar DPP-4 inhibitory activity to YE4-CFE. UHPLC-MS/MS identified 19 compounds with a relative proportion of more than 1% in the <3 kDa fraction, and adenine, acetylcholine, and L-phenylalanine were the top three substances in terms of proportion. Altogether, the inhibitory effect of YE4-CFE on DPP-4 was associated with the TNF and MAPK signaling pathways, and with the high proportion of adenine, acetylcholine, and L-phenylalanine.

Extensive Assessment of Underlying Etiological Factors in Primary Infertile Men Reduces the Proportion of Men With Idiopathic Infertility

ObjectiveUp to 40% of infertile men remain without a recognized cause (i.e., idiopathic infertility). We aimed to identify, categorize, and report the supposed causes of male infertility in a cohort of white-European men presenting for primary couple’s infertility, by using a thorough and extensive baseline diagnostic work-up.Material and MethodsCross-sectional study of 1,174 primary infertile men who underwent a thorough diagnostic work-up including: detailed medical history, physical examination, hormonal assessment, genetic testing, semen analyses; semen and urine cultures; testis color Duplex US. Men without any identified causal factor were considered as idiopathic. Six different etiological categories were established, and their prevalence was estimated. Logistic regression models estimated the risk of missing causal identification.ResultsA possible causal factor was identified in 928 (81%) men. Hypogonadism was the most frequent identified cause (37%), followed by varicocele (27%). Genetic abnormalities were found in 5% of patients. A causal factor was more easily identifiable for the more severe infertility cases, and azoospermic men were those less likely to be defined as idiopathic (OR and 95% CIs: 0.09; 0.04-0.20). Relative proportion of identified causes remained constant during the 10-year study period (p&gt;0.43).ConclusionsDue to a more comprehensive and extensive diagnostic work-up, at least one underlying cause of male infertility factor in 4 out of 5 infertile men can be identified. Men with a less severe phenotype remain a clinical challenge in terms of establishing a possible etiologic factor. Further studies are needed to assess which subset of infertile men deserves a more extensive work-up.

Deterministic Dual Control of Phase Competition in Strained BiFeO3: A Multiparametric Structural Lithography Approach

The realization of a mixed-phase microstructure in strained BiFeO3 (BFO) thin films has led to numerous novel effects derived from the coexistence of the tetragonal-like monoclinic phase (T phase) and rhombohedral-like monoclinic phase (R phase). Strong strain and polarization differences between the phases should result in a high level of transformation plasticity, which enables the continuous alteration of the relative proportion of R and T states in response to external forces. Although the potential for utilizing such plasticity to control mixed-phase populations under external stimuli is evident, direct experimental evidence backed by equilibrium predictions has not yet been fully demonstrated. Here we demonstrate deterministic control of mixed-phase populations in an epitaxially strained BFO thin film through the application of localized stresses and electric fields in a reversible manner. The results illustrate and rationalize deterministic control of mixed phases in strained BFO films, which could be crucial in tuning their functional properties. The findings also highlight a new multiparametric technique in the scanning probe lithography toolbox based on tip-assisted electric and strain field manipulation of functional properties that might find application beyond the ferroelectric domain and structural phase lithography.

Sixty years of gender representation in children’s books: Conditions associated with overrepresentation of male versus female protagonists

As a reflection of prominent cultural norms, children’s literature plays an integral role in the acquisition and development of societal attitudes. Previous reports of male overrepresentation in books targeted towards children are consistent with a history of gender disparity across media and society. However, it is unknown whether such bias has been attenuated in recent years with increasing emphasis on gender equity and greater accessibility of books. Here, we provide an up-to-date estimate of the relative proportion of males and females featured as single protagonists in 3,280 children’s books (0–16 years) published between 1960–2020. We find that although the proportion of female protagonists has increased over this 60-year period, male protagonists remain overrepresented even in recent years. Importantly, we also find persistent effects related to author gender, age of the target audience, character type (human vs. non-human), and book genre (fiction vs. non-fiction) on the male-to-female ratio of protagonists. We suggest that this comprehensive account of the factors influencing the rates of appearance of male and female protagonists can be leveraged to develop specific recommendations for promoting more equitable gender representation in children’s literature, with important consequences for child development and society.

Visual imagery vividness declines across the lifespan

The capacity to elicit vivid visual mental images varies within an extensive range across individuals between hyper- and aphantasia. It is not clear, however, whether imagery vividness is constant across the lifespan or changes during development and later in life. Without enforcing the constraints of strict experimental procedures and representativity across the entire population, our purpose was to take a first look at the self-reported level of imagery vividness and determine the relative proportion of aphantasic/hyperphantasic participants in different age-groups. Relying on the frequently used Vividness of Visual Mental Imagery questionnaire, we collected data on a random sample of 2252 participants between the ages of 12 to 60 years. We found a novel developmental pattern describing a declining ability to elicit vivid visual mental images in the group averages of different age-groups from adolescence to middle age. This effect involves both a decreasing proportion of individuals with very vivid imagery and an increasing proportion of individuals with weak imagery as maturation (assessed by boneage estimations in adolescents) and aging progresses. This finding may help to shed light on yet unknown developmental mechanisms of our internal, stimulus-independent processes, and might also help to determine genetic, maturational, and age-dependent factors in the extreme cases of hyper- and aphantasia.