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Abstract Background Occurrence of blood and meat inclusions is an internal egg quality defect. Mass candling reveals most of the spots, but because brown eggshell hampers selection in brown chicken lines it has not been possible to eliminate the defect by selection. Estimated frequency of blood and meat inclusions in brown layers is about 18% whereas it is 0.5% in white egg layers. Several factors are known to increase the incidence of this fault: genetic background, low level of vitamin A and/or D, stress or infections, for instance. To study the genetic background of the defect, a mapping population of 1599 F2 hens from a cross of White Rock and Rhode Island Red lines was set up. Results Our histopathological analyses show that blood spots consist of mainly erythrocytes and that meat spots are accumulations of necrotic material. Linkage analysis of 27 chromosomes with 162 microsatellite markers revealed one significant quantitative trait locus (QTL) affecting blood spot and meat spot frequency. We sequenced a fragment of a candidate gene within the region, ZO-2, coding for a tight junction protein. Nine polymorphisms were detected and two of them were included in fine-mapping and association analysis. Fine-mapping defined the QTL result. To further verify the QTL, association analyses were carried out in two independent commercial breeding lines with the marker MCW241 and surrounding SNPs. Association was found mainly in a 0.8 Mb-wide chromosomal area on GGAZ. Conclusions There was good agreement between the location of the QTL region on chromosome Z and the association results in the commercial breeds analyzed. Variations found in tight junction protein ZO-2 and microRNA gga-mir-1556 may predispose egg layers to blood and meat spot defects. This paper describes the first results of detailed QTL analyses of the blood and meat spots trait(s) in chickens.

Beak shape varies considerably within and between intact-beak laying hens, and aspects of beak shape appear to be heritable. As an alternative to beak treatment (an effective method of reducing damage from severe feather pecking (SFP)), this variation could be used to genetically select hens whose beak shapes are less apt to cause damage. To be able to select certain phenotypes, the beak shape variation that exists within laying hen flocks must first be characterized. The objectives of this study were to 1) describe the maxillary beak shape variation in 2 pure White Leghorn layer lines with intact beaks using geometric morphometrics to analyze images, and 2) examine the beak shape's relationship to the premaxillary bone, feather cover, and mortality. A lateral head image was taken of each hen (n = 710), and 20 landmarks were placed along each image's dorsal and ventral margins of the maxillary beak. Landmark coordinates were standardized by Procrustes superimposition, and the covariation was analyzed by principal components analysis and multivariate regression. Feather cover was scored at 3 ages and mortality was monitored throughout the production cycle. Three principal components (PCs) explained 83% of the maxillary beak shape variation and the first PC partially separated the 2 lines. Maxillary beak shapes ranged from long and narrow with pointed tips to short and wide with more curved tips. Moderate correlations were found between the maxillary beak and premaxillary bone shape (r s = 0.44) and size (r s = 0.52). Line A hens had better feather cover than Line B at all ages. Line A hens also had less total and cannibalism-related mortality than Line B (10.7 and 0.4% vs. 16.7 and 2.4%, respectively). Beak shape may be one factor contributing to the observed differences in feather cover and mortality. The results suggest that distinct maxillary beak phenotypes within each line could be selected to help reduce SFP damage and improve bird welfare. [ABSTRACT FROM AUTHOR]

Abstract: Low-frequency dielectric spectroscopy can be measured in terms of a conductance and a phase lag between the electrical current and the electrical field. This conductance and phase lag can be written as into a complex conductivity with both an in-phase and quadrature components that are frequency dependent. In sands, the low-frequency (10mHz–40kHz) spectra of the complex conductivity are dominated by the polarization of the electrical double layer (especially the internal part of the electrical double layer called the Stern layer) and the Maxwell–Wagner polarization (typically above 100Hz). We present a polarization that is able to explain the complex conductivity spectra including the grain size distribution, the porosity, and the complexation of the mineral surface with the ions of the pore water. To test this model, we investigate the sorption of various cations (Na, Pb, Zn) characterized by different affinities with the surface of silica. Sand column experiments were carried out to see the change in the complex conductivity during the advective/dispersive transport of a lead nitrate solution and a zinc sulfate solution, replacing a sodium chloride solution in the pore space of the sand. The complex conductivity model is able to explain the change of the phase over time. [Copyright &y& Elsevier]

Beak treatment is an effective method of reducing the damage inflicted by severe feather pecking (SFP) but there is significant pressure to eliminate these treatments and rely solely on alternative strategies. Substantial variation in beak shape exists within non-beak treated layer flocks and beak shape appears to be heritable. There is the potential to use this pre-existing variation and genetically select for hens whose beak shapes are less apt to cause damage during SFP. To do this, we must first understand the range of phenotypes that exist for both the external beak shape and the bones that provide its structure. The objective of this study was to determine the variation in premaxillary (within the top beak) and dentary (within the bottom beak) bone morphology that exists in 2 non-beak treated pure White Leghorn layer lines using geometric morphometrics to analyze radiographs. Lateral head radiographs were taken of 825 hens and the premaxillary and dentary bones were landmarked. Landmark coordinates were standardized by Procrustes superimposition and the covariation was analyzed by principal components analysis and multivariate regression using Geomorph (an R package). Three principal components (PCs) explained 85% of total premaxillary bone shape variation and showed that the shape ranged from long and narrow with pointed bone tips to short and wide with more curved tips. Two PCs explained 81% of total dentary bone shape variation. PC1 described the dentary bone length and width and PC2 explained the angle between the bone tip and its articular process. For both bones, shape was significantly associated with bone size and differed significantly between the two lines. Bone size accounted for 42% of the total shape variation for both bones. Together, the results showed a range of phenotypic variation in premaxillary and dentary bone shape, which in turn may influence beak shape. These bone phenotypes will guide further quantitative genetic and behavioral analyses that will help identify which beaks shapes cause the least damage when birds engage in SFP. [ABSTRACT FROM AUTHOR]

Presents research which described a system in which chirality can be varied continuously and controllably in micrometer-scale structures. Chirality in biological structures; Problem of quantitative prediction of large-scale chirality; Formation of twisted ribbons; Tuning the degree of twist and the pitch of the ribbons; Practical value of research.

Complex conductivity measurements of carbonate rocks are scarce despite the occurrence of these rocks at the surface of the Earth. The complex conductivity spectra of 57 carbonate samples were measured in a broad frequency range and at four salinities (NaCl). A simple model of induced polarization is developed to be applied to induced polarization measurements in the field. The in‐phase conductivity (related to conduction) is reported as a function of the pore water conductivity to determine the (intrinsic) formation factor and the surface conductivity. The surface conductivity and the normalized chargeability are linearly correlated to the specific surface area divided by the tortuosity of the pore space. This observation is consistent with a dynamic Stern layer polarization model, the Stern layer being the inner layer of the electrical double layer coating the grains. The quadrature conductivity is observed to be proportional to the measured normalized chargeability in agreement with the prediction of the constant phase model. The effect of the texture is discussed and we observe a power‐law relationship between the permeability and the formation factor. Then, we illustrate how this model can be applied to field data performed over a carbonate syncline in the French Alps. A 1.9 km long profile is used to separate the glacial till infilling the depression from the underlying limestones in terms of induced polarization properties. The induced polarization survey allows imaging the water content and the specific surface area of the formations down to a depth of 220 m. Key Points: The surface of carbonate grains is charged and therefore susceptible to get polarized in an electrical fieldCarbonate rocks display induced polarization in the laboratory and in the fieldThe polarization of carbonates is explained by the dynamic Stern layer concept [ABSTRACT FROM AUTHOR]

Selection to reduce susceptibility to Enterococcus faecalis infection in laying hens may contribute to the prevention of amyloid arthropathy since it is mainly induced by this bacterium. Therefore, the aim of the present study was to investigate the possibility to select more laying hens that are resistant against E. faecalis infection through the embryo lethality assay (ELA), which is proposed as an alternative model to replace the adult avian challenge assay. Ten-day-old embryos of 500 Lohmann Brown layers were inoculated into the allantoic cavity with an infectious dose of 2.5 colony-forming units (cfu)/mL of the avian E. faecalis strain K923/96 in 3 ELAs. The embryonic mortality rate (EMR) was determined by candling the eggs daily over a period of 4 d. The average EMR estimated during the 3 ELAs was 50% and the highest EMR occurred 3 to 4 d post inoculation. The estimated heritability for embryonic survivability to the infection was h2 = 0.12–0.14, calculated with the logistic and probit link function, respectively, indicating that the selection of more laying hens that are resistant to E. faecalis infection is feasible. A highly negative genetic correlation was estimated between embryonic survivability and laying performance at the peak of lay (rg = –0.22) and at the end of the production (rg = –0.65), as well as with breaking strength (rg = –0.30 to –0.37). A positive correlation was found between egg weight and the embryonic survivability (rg = +0.16), and no genetic correlation was found with body weight and dynamic stiffness. Therefore, although it was demonstrated that it is possible to breed for E. faecalis resistance, special care should be taken to monitor and to take all traits and their genetic correlations into account in order to achieve a balanced genetic progress. Besides, the ELA does not require that the hens are exposed to pathogens thereby saving labor and cost. Therefore, it could be feasible that ELA be implemented in selection programs. [ABSTRACT FROM AUTHOR]

Summary: Compromised eggshell quality causes considerable economic losses for the egg industry. Breeding for improved eggshell quality has been very challenging. Eggshell quality is a trait that would greatly benefit from marker‐assisted selection, which would allow the selection of sires for their direct contribution to the trait and would also allow implementation of measurements integrating a number of shell parameters that are difficult to measure. In this study, we selected the most promising autosomal quantitative trait loci (QTL) affecting eggshell quality on chromosomes 2, 3, 6 and 14 from earlier experiments and we extended the F2 population to include 1599 F2 females. The study was repeated on two commercial populations: Lohmann Tierzucht Rhode Island Red line (n = 692 females) and a Hy‐Line White Plymouth Rock line (n = 290 progeny tested males). We analyzed the selected autosomal QTL regions on the three populations with SNP markers at 4–13 SNPs/Mb density. QTL for eggshell quality were replicated on all studied regions in the F2 population. New QTL were detected for eggshell color on chromosomes 3 and 6. Marker associations with eggshell quality traits were validated in the tested commercial lines on chromosomes 2, 3 and 6, thus paving the way for marker‐assisted selection for improved eggshell quality. [ABSTRACT FROM AUTHOR]

Washover deposits are among the most remarkable sedimentary signatures of dune breaching and coastal inundation. Overwash of the barrier leading to washover development can be related either to storms or tsunamis but the distinction between these two processes based on the depositional record is still a matter of debate. Hence, studying recent well-documented washover deposits, combining sedimentological and hydrodynamic investigations is a key approach to identify the processes governing the washover deposition and to analyze their sediment record within the washover. During the winter of 2013–2014, the coasts of the Bay of Biscay experienced an exceptional wave climate, leading to dune breaching and washover deposition at many locations, including the Gatseau Spit (South of Oléron Island, France). Field observations, aerial photographs, topographic measurements, GPR investigations, trenches and cores, grain size analysis and magnetic fabric measurements were carried out and complemented with hydrodynamic modeling of tides, storm surges, short waves and infra gravity waves in order to compute maximum runup during the winter of 2013–2014. Such an interdisciplinary approach led to propose that: (1) large overwash events occurring during the winter of 2013–2014 were mainly driven by infra gravity (IG) waves combined with high tides; (2) the washover elongated outer shape was strongly controlled by the antecedent morphology of the back-barrier area; (3) one overwash flow driven by one IG wave is recorded by one normally graded lamina composed of quartz sand at base and heavy minerals enriched sand at top; (4) dominant settling of the particles from a suspension during sedimentation occurred in the end of each overwash flow in response to flow velocity decrease; (5) laminae can be grouped in laminasets generally composed of thinning upward laminae, related to overwash flow depth decrease during falling tide and to erosion of basal laminae by highest overwash flows occurring more likely around the high tide; (6) the number of laminasets in a proximal position is in the same order of magnitude as the number of modeled highest runup events, offering an almost complete record of overwash events that occurred during the winter 2013–2014. [ABSTRACT FROM AUTHOR]

Little is known about the fluctuations of the Pyrenean glaciers. In this study, we reconstructed the evolution of Ossoue Glacier (42°46'N, 0.45 km&178;), which is located in the central Pyrenees, from the Little Ice Age (LIA) onwards. To do so, length, area, thickness, and mass changes in the glacier were generated from historical data sets, topographical surveys, glaciological measurements (2001-2013), a ground penetrating radar (GPR) survey (2006), and stereoscopic satellite images (2013). The glacier has receded considerably since the end of the LIA, losing 40 % of its length and 60 % of its area. Three periods of marked ice depletion were identified: 1850-1890, 1928-1950, and 1983-2013, as well as two short periods of stabilization: 1890-1894, 1905-1913, and a longer period of slight growth: 1950-1983; these agree with other Pyrenean glacier reconstructions (Maladeta, Coronas, Taillon glaciers). Pyrenean and Alpine glaciers exhibit similar multidecadal variations during the 20th century, with a stable period detected at the end of the 1970s and periods of ice depletion during the 1940s and since the 1980s. Ossoue Glacier fluctuations generally concur with climatic data (air temperature, precipitation, North Atlantic Oscillation, Atlantic Multidecadal Oscillation). Geodetic mass balance over 1983-2013 was -1.04 ± 0.06 w.e.a-1 (-31.3 ± 1.9 mw.e.), whereas glaciological mass balance was -1.45 ± 0.85 mw.e. a-1 (-17.3 ± 2.9 mw.e.) over 2001-2013, resulting in a doubling of the ablation rate in the last decade. In 2013 the maximum ice thickness was 59 ± 10.3 m. Assuming that the current ablation rate remains constant, Ossoue Glacier will disappear midway through the 21st century. [ABSTRACT FROM AUTHOR]

Egg quality traits are of utmost importance in layer breeding programs due to their effect on profitability in the egg production industry and on the production of quality chicks. Therefore, the aim of this study was to analyze and estimate genetic parameters of different quality traits: egg weight, breaking strength, dynamic stiffness (Kdyn), egg shape index, eggshell thickness, and albumen height. Eggs were obtained from 4 pure lines of birds. Two different tests were performed: a white breeding program, with eggs from a male and female line of a white egg layer program that were analyzed at 67 to 70 wk of age, and a brown breeding program, with eggs from a male and female line of a brown egg layer program that were analyzed at 32 to 36 wk of age. In general, heritabilities were moderate to high for all traits (h2 = 0.23 to 0.71). A high genetic correlation was estimated in both tests between breaking strength and Kdyn (rg = +0.40 to +0.61). Shell thickness was also positively correlated with breaking strength (rg = +0.50 to +0.63) and Kdyn (rg = +0.28 to +0.69). These moderate relationships demonstrate that the strength of an egg not only relies on the shell thickness but also on the quality and uniformity of eggshell construction. Dynamic stiffness might be preferred for breeding purposes due to its lower negative genetic correlation with egg weight and its higher heritability (h2 = 0.35 to 0.70) compared with breaking strength (h2 = 0.23 to 0.35). Breaking strength and Kdyn were positively correlated with shape index, which confirms that round eggs will show higher shell stability. Therefore, it is necessary to monitor egg shape to maintain an optimal form. [ABSTRACT FROM AUTHOR]

1. The responses to genetic selection on yolk proportion as a technique for increasing egg dry matter content, an important criterion for the egg-product industry, was investigated in a pedigree flock of White Leghorn hens. 2. Parents were preselected on high and low yolk proportion from a base population. The absolute estimated breeding value for yolk proportion of both groups differed by 3%. The realised selection difference in dry matter content of eggs between groups was more than 1% in the analysed offspring population. 3. Heritability estimates were moderate and dry matter had a lower heritability (h2 = 0.39) than yolk proportion (h2 = 0.44). 4. The genetic correlation between yolk proportion and dry matter content was highly positive (rg= 0.91). Genetic correlations with egg weight were negative and would have to be compensated for in a breeding programme (rg = −0.76 with yolk proportion andrg = −0.64 with dry matter content). The genetic correlation between the laying performance and yolk proportion wasrg = 0.28 and close to zero (rg = −0.05) for dry matter content. 5. Easy recording and lower undesirable correlations make yolk proportion more suitable for commercial selection compared with egg dry matter content in layer breeding. [ABSTRACT FROM AUTHOR]

The cuticle is a proteinaceous layer covering the avian egg and is believed to form a defence to microorganism ingress. In birds that lay eggs in challenging environments, the cuticle is thicker, suggesting evolutionary pressure; however, in poultry, selection pressure for this trait has been removed because of artificial incubation. This study aimed to quantify cuticle deposition and to estimate its genetic parameters and its role on trans-shell penetration of bacteria. Additionally, cuticle proteins were characterised to establish whether alleles for these genes explained variation in deposition. A novel and reliable quantification was achieved using the difference in reflectance of the egg at 650 nm before and after staining with a specific dye. The heritability of this novel measurement was moderate (0.27), and bacteria penetration was dependent on the natural variation in cuticle deposition. Eggs with the best cuticle were never penetrated by bacteria ( P < 0.001). The cuticle proteome consisted of six major proteins. A significant association was found between alleles of one of these protein genes, ovocleidin-116 ( MEPE), and cuticle deposition ( P = 0.015) and also between alleles of estrogen receptor 1 ( ESR1) gene and cuticle deposition ( P = 0.008). With the heritability observed, genetic selection should be possible to increase cuticle deposition in commercial poultry, so reducing trans-generational transmission of microorganisms and reversing the lack of selection pressure for this trait during recent domestication. [ABSTRACT FROM AUTHOR]

The size and orientation of calcium carbonate crystals influence the structure and strength of the eggshells of chickens. In this study, estimates of heritability were found to be high (0.6) for crystal size and moderate (0.3) for crystal orientation. There was a strong positive correlation (0.65) for crystal size and orientation with the thickness of the shell and, in particular, with the thickness of the mammillary layer. Correlations with shell breaking strength were positive but with a high standard error. This was contrary to expectations, as in man-made materials smaller crystals would be stronger. We believe the results of this study support the hypothesis that the structural organization of shell, and in particular the mammillary layer, is influenced by crystal size and orientation, especially during the initial phase of calcification. Genetic associations for crystal measurements were observed between haplotype blocks or individual markers for a number of eggshell matrix proteins. Ovalbumin and ovotransferrin ( LTF) markers for example were associated with crystal size, while ovocleidin-116 and ovocalyxin-32 ( RARRES1) markers were associated with crystal orientation. The location of these proteins in the eggshell is consistent with different phases of the shell-formation process. In conclusion, the variability of crystal size, and to a lesser extent orientation, appears to have a large genetic component, and the formation of calcite crystals are intimately related to the ultrastructure of the eggshell. Moreover, this study also provides evidence that proteins in the shell influence the variability of crystal traits and, in turn, the shell's thickness profile. The crystal measurements and/or the associated genetic markers may therefore prove to be useful in selection programs to improve eggshell quality. [ABSTRACT FROM AUTHOR]

Good eggshell quality is important for both table egg quality and chicken reproductive performance. Weak eggshells cause economic losses in all production steps. Poor eggshell quality also poses increased risk for Salmonella infections. Eggshell quality has been a difficult trait to improve by traditional breeding, as it can be measured only for females and it is difficult and expensive to measure. Breeding for improved shell quality may therefore benefit from the use of marker-assisted selection. In an effort to find markers linked to eggshell quality, we have used an F population of 668 females to map quantitative trait loci (QTL) affecting eggshell traits (eggshell deformation, breaking force, weight). By using 160 microsatellite markers on 27 chromosomes, we found 11 genome-wide and 15 suggestive QTL for shell traits measured at different times during production. Loci affecting the deformation were found on chromosomes 1, 2, 6, 10, 14 and Z. Loci affecting the breaking force were detected on chromosomes 2, 3, 10, 12 and Z. Loci affecting the shell weight were detected on chromosomes 6, 12, 24 and Z. Each QTL explains between 1.5% and 4.6% of the phenotypic variance, adding up to 10-15% of total phenotypic variance explained for the different traits. No epistatic effects were observed between loci affecting eggshell traits. Because the effects for quality are mainly additive, these results provide a basis for further characterization of the loci to identify closely linked markers to be used in marker-assisted selection. [ABSTRACT FROM AUTHOR]

Abstract: Seven well-characterized clay-rocks have been taken from three test sites to perform spectral induced polarization (SIP) measurements during desiccation of these samples. These test sites include (1) the Tournemire site (IRSN) located in south of France, (2) The Bure test site (ANDRA) located in west of France, and (3) the Super-Sauze earthflow located in south western of France. We dried the samples at ambient temperature followed by heating between 65 °C and 105 °C. The quadrature conductivity, at very low-frequency, was able to discriminate between the loss of free water from the macropores and the loss of water in the micropores associated with textural changes. The calcite and quartz grain size distributions had a significant effect on the low-frequency spectrum. The inversion of our SIP data demonstrated that the generalized Cole–Cole model is an appropriate empirical and practical model for monitoring changes in water content of clay-rocks. [Copyright &y& Elsevier]

Novel and traditional eggshell quality measurements were made from up to 2000 commercial pedigree hens for a candidate gene association analysis with organic eggshell matrix genes: ovocleidin-116, osteopontin ( SPP1), ovocalyxin-32 ( RARRES1), ovotransferrin ( LTF), ovalbumin and ovocalyxin-36, as well as key genes in the maintenance and function of the shell gland [ estrogen receptor ( ESR1) and carbonic anhydrase II ( CAII)]. Associations were found for (i) ovalbumin with breaking strength and shell thickness; (ii) ovocleidin-116 with elastic modulus, shell thickness and egg shape; (iii) RARRES1 with mammillary layer thickness; (iv) ESR1 with dynamic stiffness; (v) SPP1 with fracture toughness and (vi) CAII with egg shape. The marker effects are as large as 17% of trait standard deviations and could be used to improve eggshell quality. [ABSTRACT FROM AUTHOR]

1. The study was conducted to estimate the heritability, genetic correlations and breeding values of laying hens based on individual records and group mean records. 2. Records of two pure lines from a commercial breeding programme of White Leghorns from three generations housed in single cages and in group cages were used. A total of 8483 and 8817 individual records of lines A and D, respectively, and a total of 1358 (line A) and 1161 (line D) group mean records were analysed. 3. An animal model using Restricted Maximum Likelihood (REML) was used to estimate variance components of individual records. Group mean records were analysed using the sire model, taking heterogeneity of error variance and correlated residual effects into account. Breeding values of sires were estimated based on the BLUP method using a multivariate sire model. Spearman Rank correlations were used to compare sire breeding values estimated from individual records and from group mean records. The traits studied were monthly egg production, cumulative production and egg weight. 4. Heritability estimates based on individual records were higher than from group mean records. Heritabilities for cumulative production records were higher than for monthly production, based on individual as well as group mean records. The estimates of genetic correlations between monthly egg production and cumulative production were moderate to high. Egg production and egg weight recorded individually were highly genetically correlated with those recorded on group means. Sire breeding values estimated from individual records showed high correlations with those from group mean records. 5. Differences in the ranking of sire breeding values estimated from individual vs group mean records were negligible, indicating that no genotype × environment interaction exists. Selection based on individual performance records of laying hens housed in single cages could give a good response on performance of laying hens housed in group cages. Cumulative egg production over periods 1 to 6 is the best trait for the selection programme. [ABSTRACT FROM AUTHOR]

Searching for recyclable materials of construction, in the objective of building sobriety and resilience, is a major issue of our current societies. Mudbricks of compacted rammed earth represent an ancient construction material with many advantages associated with its availability, cost of production, potential reuse, and with a very low carbon footprint. Moisture content affects the mechanical resistance of such materials, which could become mechanically weak above a critical value. Therefore, non-intrusive characterization techniques able to image the water content distribution of these materials is highly in demand. We apply a recently developed theory of complex electrical conductivity (alias induced polarization) to characterize core samples of rammed earth materials in the laboratory. Complex conductivity describes both the ability of a porous material to conduct an electrical current (characterized by the in-phase conductivity) and its ability to store reversibly electrical charges (characterized by two interconnected properties namely the quadrature conductivity and the normalized chargeability). Samples of rammed earth and clayey soils with different pore water salinities, saturations, and compaction states are measured with the complex conductivity method in the frequency range 100 mHz–45 kHz. The in-phase and quadrature conductivities of the complex conductivity of rammed earth are connected to the water content offering therefore a new non-intrusive tomographic technique to study the water content distribution in walls made of rammed earth. The data are all consistent with the so-called dynamic Stern layer model of complex conductivity for clayey materials. This new approach provides a general method to image the change in the water content of walls made of rammed earth, a task that electrical conductivity imaging cannot perform as a stand-alone technique. • There is a growing need for imaging the water content variations of walls made of rammed earth. • Induced polarization is a non-intrusive imaging technique that can be used for this task. • Laboratory tests are used to understand the complex conductivity of rammed earth and clayey soils. [ABSTRACT FROM AUTHOR]

Strontium-doped ZnS nanoparticles (NPs) (1.5, 5 and 9 wt%) were synthesized through a surfactant free hydrothermal method. The structural characterization by X-ray diffraction confirms the synthesis of ZnS, with its two crystalline phases (cubic and hexagonal), without apparition of any peaks related to Sr phases. The crystallite size is affected by Sr doping concentration and was estimated in the range of 2.24–2.51 nm. Furthermore, transmission electron microscopy images show that the NPs have great tendency to aggregate into spherical shapes. Spectroscopy analysis revealed vibration modes specific to ZnS materials on the Raman spectra at about 260 and 345 cm - 1 and on Fourier-transform infrared spectra at 668.9 cm - 1 . Electronic investigation performed by UV–Visible diffuse reflectance spectroscopy showed that the synthesized ZnS NPs are optically transparent in the visible domain and their band gap energy decreases from 3.42 to 3.38 eV with increasing Sr concentration. Finally, the methyl orange degradation rate increases with Sr concentration, revealing an improvement in the photocatalytic properties of Sr-doped ZnS NPs. [ABSTRACT FROM AUTHOR]

Peptides are well known for forming nanoparticles, while DNA duplexes, triplexes and tetraplexes create rigid nanostructures. Accordingly, the covalent conjugation of peptides to DNA/RNA produces hybrid self-assembling features and may lead to interesting nano-assemblies distinct from those of their individual components. Herein, we report the preparation of a collagen mimetic peptide incorporating lysine in its backbone, with alkylamino side chains radially conjugated with G-rich PNA [collagen-(PNA-GGG) 3 ]. In the presence of complementary C-rich DNA (dCCCTTTCCC) at neutral pH, the collagen mimetic triplexes were interconnected by PNA-GGG : DNA-CCC duplexes, leading to the formation of larger assemblies of nanostructures. Upon decreasing the pH to 4.5, the dissociation of the triplex-duplex assembly released the protonated C-rich DNA, which immediately folded into an i -motif. With an increase in the pH to 7.2 (neutral), the i -motif unfolded into linear DNA, which reformed the PNA-GGG : DNA-CCC duplex interconnecting the collagen triplexes. The pH-induced switching of the assembly and disassembly was reversible over a few cycles. The hybrid collagen-(PNAGGG) 3  : DNA-C 3 T 3 C 3 triplex-duplex and the individual components of the assembly including the i -motif were characterized by UV and CD melting, fluorescence, TEM and gel electrophoresis. The pH-induced reversible switching was established by the changes in the CD and fluorescence properties. Peptide-DNA conjugates have wide applications in both biology and materials science, ranging from therapeutics and drug delivery to diagnostics and molecular switches. Thus, the prototype ensemble of the triplex peptide-PNA conjugate and its duplex with DNA described herein has potential for elaboration into rationally designed systems by varying the PNA/DNA sequences to trap functional ligands/drugs for release in pH-controlled environments.

Short peptide-based supramolecular hydrogels appeared as highly interesting materials for applications in many fields. The optimization of their properties relies mainly on the design of a suitable hydrogelator through an empirical trial-and-error strategy based on the synthesis of various types of peptides. This approach is in part due to the lack of prior structural knowledge of the molecular architecture of the various families of nanofibers. The 3D structure of the nanofibers determines their ability to interact with entities present in their surrounding environment. Thus, it is important to resolve the internal structural organization of the material. Herein, using Fmoc-FFY tripeptide as a model amphiphilic hydrogelator and cryo-EM reconstruction approach, we succeeded to obtain a 3.8 Å resolution 3D structure of a self-assembled nanofiber with a diameter of approximately 4.1 nm and with apparently "infinite" length. The elucidation of the spatial organization of such nano-objects addresses fundamental questions about the way short amphiphilic N -Fmoc peptides lacking secondary structure can self-assemble and ensure the cohesion of such a lengthy nanostructure. This nanofiber is organized into a triple-stranded helix with an asymmetric unit composed of two Fmoc-FFY peptides per strand. The three identical amphiphilic strands are maintained together by strong lateral interactions coming from a 3-Fmoc zipper motif. This hydrophobic core of the nanofiber is surrounded by 12 phenyl groups from phenylalanine residues, nonplanar with the six Fmoc groups. Polar tyrosine residues at the C-term position constitute the hydrophilic shell and are exposed all around the external part of the assembly. This fiber has a highly hydrophobic central core with an internal diameter of only 2.4 Å. Molecular dynamics simulations highlight van der Waals and hydrogen bonds between peptides placed on top of each other. We demonstrate that the self-assembly of Fmoc-FFY, whether induced by annealing or by the action of a phosphatase on the phosphorylated precursor Fmoc-FF p Y, results in two nanostructures with minor differences that we are unable to distinguish.

Undifferentiated embryonal sarcoma of the liver is a rare mesenchymal malignancy that predominantly occurs in children. The relationship between this tumor entity and germline pathogenic variants (PVs) remains undefined. Here, we present the clinical case of a male patient diagnosed with undifferentiated embryonal sarcoma of the liver. Both germline and tumor samples were analyzed using next-generation sequencing. In the tumor tissue, PVs in TP53 (NM&#95;000546.5):c.532del p.(His178Thrfs*69) and CHEK2 (NM&#95;007194.4):c.85C>T p.(Gln29*) were identified, with both confirmed to be of germline origin. Copy number analyses indicated a loss of the wildtype TP53 allele in the tumor, consistent with a second hit, while it was the variant CHEK2 allele that was lost in the tumor. Our data indicate that the germline TP53 PV acts as a driver of tumorigenesis in the reported case and support a complex interaction between the germline TP53 and CHEK2 PVs. This case highlights the dynamic interplays of genetic alterations in tumorigenesis and emphasizes the need for continued investigation into the complex interactions between TP53 and CHEK2 PVs and into the association of undifferentiated embryonal sarcoma of the liver and Li-Fraumeni syndrome.

Enzymatically-active polyelectrolyte multilayers containing n layers of phosphatase (AP n -PEM) induce the formation of supported biocatalytic supramolecular hydrogels when brought in contact with the precursor tripeptide Fmoc-FFpY (Fmoc = N-fluorenylmethyloxycarbonyl; F = Phenylalanine; Y = Tyrosine; p = phosphate group). AP n -PEM triggers the spatially-localized hydrogelation reaching 2, 17 and 350 µm of thickness for n = 1, 2 and 3, respectively. As observed by cryo scanning electron microscopy, a dense nanofibrous network underpinning the hydrogel shows parallelly orientated Fmoc-FFY peptide-based fibrils, perpendicular to the substrate. For the gel generated by the AP 3 -PEM, fluorescence confocal microscopy images show that during the peptide self-assembly, some enzymes are distributed in the hydrogel, preferentially located in few dozens of micrometers above the substrate. In addition, a self-assembly growth rate of 5 µm min -1 is determined when the hydrogelation starts. Through transmission electron microscopy immuno-labelling experiments on self-assemblies generated in solution, we observe that AP are decorating the Fmoc-FFY nanofibers. It is observed both a long-term stability and a higher biocatalytic activity of the so AP-encapsulated hydrogel compared to the bare AP n -PEM. This bioactivity can be tuned by the number n in batch and under continuous flow conditions. To illustrate the versatility of this enzyme-supported strategy, multi-catalytic transformations in continuous flow conditions have been successfully carried out using supported supramolecular hydrogel., (© 2024 Wiley‐VCH GmbH.)

Recently, we have investigated the enzyme-assisted self-assembly of precursor peptides diffusing in an enzyme-containing host gel, leading to various self-assembly profiles within the gel. At high enzyme concentrations, the reaction-diffusion self-assembly processes result in the formation of a continuous non-monotonous peptide self-assembly profile. At low enzyme concentrations, they result in the formation of individual self-assembled peptide microglobules and at intermediate enzyme concentrations both kinds of self-assembled structures coexist. Herein, we develop a Liesegang-type model that considers four major points: (i) the diffusion of the precursor peptides within the host gel, (ii) the diffusion of the enzymes in the gel, (iii) the enzymatic transformation of the precursor peptides into the self-assembling ones and (iv) the nucleation of these building blocks as the starting point of the self-assembly process. This process is treated stochastically. Our model predicts most of the experimentally observed features and in particular (i) the transition from a continuous to a microglobular pattern of self-assembled peptides through five types of patterns by decreasing the enzyme concentration in the host hydrogel. (ii) It also predicts that when the precursor peptide concentration decreases, the enzyme concentration at which the continuous/microglobules transition appears increases. (iii) Finally, it predicts that for peptides whose critical self-assembly concentration in solution decreases, the peptide concentration at which the continuous-to-microglobular transition decreases too. All these predictions are observed experimentally.

Enteric viruses are the main cause of acute gastroenteritis worldwide with a significant morbidity and mortality, especially among children and aged adults. Some enteric viruses also cause disseminated infections and severe neurological manifestations such as poliomyelitis. Protective immunity against these viruses is not well understood in humans, with most knowledge coming from animal models, although the development of poliovirus and rotavirus vaccines has extended our knowledge. In a classical view, innate immunity involves the recognition of foreign DNA or RNA by pathogen recognition receptors leading to the production of interferons and other inflammatory cytokines. Antigen uptake and presentation to T cells and B cells then activate adaptive immunity and, in the case of the mucosal immunity, induce the secretion of dimeric IgA, the more potent immunoglobulins in viral neutralization. The study of Inborn errors of immunity (IEIs) offers a natural opportunity to study nonredundant immunity toward pathogens. In the case of enteric viruses, patients with a defective production of antibodies are at risk of developing neurological complications. Moreover, a recent description of patients with low or absent antibody production with protracted enteric viral infections associated with hepatitis reinforces the prominent role of B cells and immunoglobulins in the control of enteric virus., (© 2024 The Author(s). Immunological Reviews published by John Wiley & Sons Ltd.)

Background: Seronegative autoimmune hepatitis in children is a rare but potentially severe disease, sometimes requiring liver transplantation. This type of hepatitis may be associated with various immunological and hematological disorders, ranging from isolated lymphopenia to aplastic anemia. Precise pathophysiological mechanisms are still unknown, but the role of viruses cannot be excluded, either as directly pathogenic or as triggers, responsible for an inappropriate immune stimulation. Having the impression of an increasing number of seronegative autoimmune hepatitis since the beginning of SARS-CoV-2 pandemia period, we hypothesized that SARS-CoV-2 virus could be an infectious trigger., Methods: We conducted a retrospective, observational, descriptive study about children with seronegative autoimmune hepatitis, in a tertiary care center, between 2010 and 2022., Results: Thirty-two patients were included. The overall incidence of seronegative autoimmune hepatitis increased 3.3-fold in 2020-2022, during the SARS-CoV-2 pandemia period (16 patients in 2.8 years) compared with 2010-2019 the pre pandemia period (16 patients in 9 years). Patients' clinical and biochemical liver characteristics did not differ between the two periods. Hematological damages were less severe during the pandemia period. Immunological studies revealed a dysregulated immune response. The initiation of immunosuppressive therapy (corticosteroids ± cyclosporine) was earlier during the pandemia period than before., Conclusion: In cases of undetermined acute hepatitis, an immune-mediated origin should be considered, prompting a liver biopsy. If the histological aspect points to an immune origin, immunosuppressive treatment should be instituted even though autoimmune hepatitis antibodies are negative. Close hematological monitoring must be performed in all cases. The 3.3-fold increase of cases during the SARS-CoV-2 pandemia will need to be further analyzed to better understand the underlying immunological mechanisms, and to prove its potential involvement., 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 © 2024 Schmutz, Chartier, Leblanc, Mussini, Gardin, Gonzales, Roque-Afonso, Le Cam, Hery, Neven, Charbel, Vartanian, Jacquemin, Morelle and Almes.)

Purpose: Providing patient access to precision oncology (PO) is a major challenge of clinical oncologists. Here, we provide an easily transferable model from strategic management science to assess the outreach of a cancer center., Methods: As members of the German WERA alliance, the cancer centers in Würzburg, Erlangen, Regensburg and Augsburg merged care data regarding their geographical impact. Specifically, we examined the provenance of patients from WERA´s molecular tumor boards (MTBs) between 2020 and 2022 (n = 2243). As second dimension, we added the provenance of patients receiving general cancer care by WERA. Clustering our catchment area along these two dimensions set up a four-quadrant matrix consisting of postal code areas with referrals towards WERA. These areas were re-identified on a map of the Federal State of Bavaria., Results: The WERA matrix overlooked an active screening area of 821 postal code areas - representing about 50 % of Bavaria´s spatial expansion and more than six million inhabitants. The WERA matrix identified regions successfully connected to our outreach structures in terms of subsidiarity - with general cancer care mainly performed locally but PO performed in collaboration with WERA. We also detected postal code areas with a potential PO backlog - characterized by high levels of cancer care performed by WERA and low levels or no MTB representation., Conclusions: The WERA matrix provided a transparent portfolio of postal code areas, which helped assessing the geographical impact of our PO program. We believe that its intuitive principle can easily be transferred to other cancer centers., Competing Interests: Declaration of Competing Interest 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., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

We explore the effect of poly(ethylene glycol) (PEG) molar mass on the intrinsic permeability and structural characteristics of poly(ethylene glycol) diacrylate PEGDA/PEG composite hydrogel membranes. We observe that by varying the PEG content and molar mass, we can finely adjust the water intrinsic permeability by several orders of magnitude. Notably, we show the existence of maximum water intrinsic permeability, already identified in a previous study to be located at the critical overlap concentration C * of PEG chains, for the highest PEG molar mass studied. Furthermore, we note that the maximum intrinsic permeability follows a non-monotonic evolution with respect to the PEG molar mass and reaches its peak at 35 000 g mol -1 . Besides, our results show that a significant fraction of PEG chains is irreversibly trapped within the PEGDA matrix even for the lowest molar masses down to 600 g mol -1 . This observation suggests the possibility of covalent grafting of the PEG chains onto the PEGDA matrix. CryoSEM and AFM measurements demonstrate the presence of large micron-sized cavities separated by PEGDA-rich walls whose nanometric structures strongly depend on the PEG content. By combining our permeability and structural measurements, we suggest that the PEG chains trapped inside the PEGDA-rich walls induce nanoscale defects in the crosslinking density, resulting in increased permeability below C *. Conversely, above C *, we speculate that partially trapped PEG chains may form a brush-like arrangement on the surface of the PEGDA-rich walls, leading to a reduction in permeability. These two opposing effects are anticipated to exhibit molar-mass-dependent trends, contributing to the non-monotonic variation of the maximum intrinsic permeability at C *. Overall, our results demonstrate the potential to fine-tune the properties of hydrogel membranes, offering new opportunities for separation applications.

Nanoparticle (NP) surface functionalization with proteins, including monoclonal antibodies (mAbs), mAb fragments, and various peptides, has emerged as a promising strategy to enhance tumor targeting specificity and immune cell interaction. However, these methods often rely on complex chemistry and suffer from batch-dependent outcomes, primarily due to limited control over the protein orientation and quantity on NP surfaces. To address these challenges, a novel approach based on the supramolecular assembly of two peptides is presented to create a heterotetramer displaying V H Hs on NP surfaces. This approach effectively targets both tumor-associated antigens (TAAs) and immune cell-associated antigens. In vitro experiments showcase its versatility, as various NP types are biofunctionalized, including liposomes, PLGA NPs, and ultrasmall silica-based NPs, and the V H Hs targeting of known TAAs (HER2 for breast cancer, CD38 for multiple myeloma), and an immune cell antigen (NKG2D for natural killer (NK) cells) is evaluated. In in vivo studies using a HER2+ breast cancer mouse model, the approach demonstrates enhanced tumor uptake, retention, and penetration compared to the behavior of nontargeted analogs, affirming its potential for diverse applications., (© 2024 The Authors. Advanced Healthcare Materials published by Wiley‐VCH GmbH.)

Background: Hypoxia is an important risk factor and indicator for the declining health of inpatients. Predicting future hypoxic events using machine learning is a prospective area of study to facilitate time-critical interventions to counter patient health deterioration., Objective: This systematic review aims to summarize and compare previous efforts to predict hypoxic events in the hospital setting using machine learning with respect to their methodology, predictive performance, and assessed population., Methods: A systematic literature search was performed using Web of Science, Ovid with Embase and MEDLINE, and Google Scholar. Studies that investigated hypoxia or hypoxemia of hospitalized patients using machine learning models were considered. Risk of bias was assessed using the Prediction Model Risk of Bias Assessment Tool., Results: After screening, a total of 12 papers were eligible for analysis, from which 32 models were extracted. The included studies showed a variety of population, methodology, and outcome definition. Comparability was further limited due to unclear or high risk of bias for most studies (10/12, 83%). The overall predictive performance ranged from moderate to high. Based on classification metrics, deep learning models performed similar to or outperformed conventional machine learning models within the same studies. Models using only prior peripheral oxygen saturation as a clinical variable showed better performance than models based on multiple variables, with most of these studies (2/3, 67%) using a long short-term memory algorithm., Conclusions: Machine learning models provide the potential to accurately predict the occurrence of hypoxic events based on retrospective data. The heterogeneity of the studies and limited generalizability of their results highlight the need for further validation studies to assess their predictive performance., (© Lena Pigat, Benjamin P Geisler, Seyedmostafa Sheikhalishahi, Julia Sander, Mathias Kaspar, Maximilian Schmutz, Sven Olaf Rohr, Carl Mathis Wild, Sebastian Goss, Sarra Zaghdoudi, Ludwig Christian Hinske. Originally published in JMIR Medical Informatics (https://medinform.jmir.org).)

Nanocomposite hydrogels were elaborated that consisted of a physical network formed by an amphiphilic polymer in which C 60 fullerene nanoplatelets were embedded. Characterization showed that the nanoplatelets within the polymer network were aggregated. The presence of these nanoplatelets led to an increase of the shear modulus of the hydrogels, that cannot be explained by a filler effect alone. The nanocomposite gels displayed similar rheological behavior, both in linear and non-linear domains, as neat hydrogels at higher polymer concentrations. We suggest that the particles reinforced the gels by forming additional connections between the polymer chains.

As the primary products of lipid oxidation, lipid hydroperoxides constitute an important class of lipids generated by aerobic metabolism. However, despite several years of effort, the structure of the hydroperoxidized bilayer has not yet been observed under electron microscopy. Here we use a 200 kV Cryo-TEM to image small unilamellar vesicles (SUVs) made (i) of pure POPC or SOPC, (ii) of their pure hydroperoxidized form, and (iii) of their equimolar mixtures. We show that the challenges posed by the determination of the thickness of the hydroperoxidized bilayers under these observation conditions can be addressed by an image analysis method that we developed and describe here., (Copyright © 2024. Published by Elsevier Inc.)

The diagnosis of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), originally based on morphological assessment alone, has to bring together more and more disciplines. Today, modern AML/MDS diagnostics rely on cytomorphology, cytochemistry, immunophenotyping, cytogenetics, and molecular genetics. Only the integration of all these methods allows a comprehensive and complementary characterization of each case, which is a prerequisite for optimal AML/MDS diagnosis and treatment. In the following, we present why multidisciplinary and local diagnosis is essential today and will become even more important in the future, especially in the context of precision medicine. We present our idea and strategy implemented at Augsburg University Hospital, which has realized multidisciplinary diagnostics in AML/MDS in an interdisciplinary and decentralized approach. In particular, this includes the recent technical advances that molecular genetics provides with modern methods. The enormous amount of data generated by these techniques represents a major challenge, but also a unique opportunity. We will reflect on how this increase in knowledge can be integrated into routine practice to lead the way for personalized medicine in AML/MDS to improve patient care., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background: Acute myeloid leukemia (AML) is a heterogeneous disease with a poor prognosis. Dysregulation of the epigenetic machinery is a significant contributor to disease development. Some AML patients benefit from treatment with hypomethylating agents (HMAs), but no predictive biomarkers for therapy response exist. Here, we investigated whether unbiased genome-wide assessment of pre-treatment DNA-methylation profiles in AML bone marrow blasts can help to identify patients who will achieve a remission after an azacytidine-containing induction regimen., Results: A total of n = 155 patients with newly diagnosed AML treated in the AMLSG 12-09 trial were randomly assigned to a screening and a refinement and validation cohort. The cohorts were divided according to azacytidine-containing induction regimens and response status. Methylation status was assessed for 664,227 500-bp-regions using methyl-CpG immunoprecipitation-seq, resulting in 1755 differentially methylated regions (DMRs). Top regions were distilled and included genes such as WNT10A and GATA3. 80% of regions identified as a hit were represented on HumanMethlyation 450k Bead Chips. Quantitative methylation analysis confirmed 90% of these regions (36 of 40 DMRs). A classifier was trained using penalized logistic regression and fivefold cross validation containing 17 CpGs. Validation based on mass spectra generated by MALDI-TOF failed (AUC 0.59). However, discriminative ability was maintained by adding neighboring CpGs. A recomposed classifier with 12 CpGs resulted in an AUC of 0.77. When evaluated in the non-azacytidine containing group, the AUC was 0.76., Conclusions: Our analysis evaluated the value of a whole genome methyl-CpG screening assay for the identification of informative methylation changes. We also compared the informative content and discriminatory power of regions and single CpGs for predicting response to therapy. The relevance of the identified DMRs is supported by their association with key regulatory processes of oncogenic transformation and support the idea of relevant DMRs being enriched at distinct loci rather than evenly distribution across the genome. Predictive response to therapy could be established but lacked specificity for treatment with azacytidine. Our results suggest that a predictive epigenotype carries its methylation information at a complex, genome-wide level, that is confined to regions, rather than to single CpGs. With increasing application of combinatorial regimens, response prediction may become even more complicated., (© 2023. The Author(s).)

Hydrogels are promising systems for separation applications due to their structural characteristics (i.e., hydrophilicity and porosity). In our study, we investigate the permeation of suspensions of rigid latex particles of different sizes through free-standing hydrogel membranes prepared by photopolymerization of a mixture of poly(ethylene glycol) diacrylate (PEGDA) and large poly(ethylene glycol) (PEG) chains of 300,000 g·mol -1 in the presence of a photoinitiator. Atomic force microscopy and cryoscanning electron microscopy (cryoSEM) were employed to characterize the structures of the hydrogel membranes. We find that the 20 nm particle permeation depends on both the PEGDA/PEG composition and the pressure applied during filtration. In contrast, we do not measure a significant permeation of the 100 nm and 1 μm particles, despite the presence of large cavities of 1 μm evidenced by the cryoSEM images. We suggest that the PEG chains induce local nanoscale defects in the cross-linking of PEGDA-rich walls separating the micrometer-sized cavities, which control the permeation of particles and water. Moreover, we discuss the decline of the permeation flux observed in the presence of latex particles compared to that of pure water. We suggest that a thin layer of particles forms on the surface of the hydrogels.

The cuticle is an invisible barrier that protects the internal egg contents from microorganisms entering through gas exchange pores. Eggs which have a good cuticle are least likely to be penetrated by microorganisms and improved cuticle cover should reduce vertical transmission of microorganisms and improve biosecurity. The aim was to carry out a genome wide association study for cuticle deposition in 3 independent populations of laying hens using tartrazine and lissamine green staining. Eggs from ∼8,000 hens represented 2 White Leghorn and 1 Rhode Island Red breed. Estimates of heritability using pedigree or genomic relationship matrices were in the 0.2 to 0.3 range. The results were breed specific. Across the populations, genomic regions on chromosomes 1, 2, 4, 5, and 8 were identified as significantly associated with cuticle deposition. No single loci had a large effect. A comparison was made with genes differentially expressed in the shell gland when cuticle deposition was manipulated, however none were obvious candidates for cuticle deposition. The results support the polygenic nature of the trait and the information will help in the future to understand the genetic variance and what might control cuticle deposition and the microbiological safety of the egg., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)