Kinetics of N- to M-Polar Switching in Ferroelectric Al1-xScxN Capacitors.

Ferroelectric wurtzite-type aluminum scandium nitride (Al1-xScxN) presents unique properties that can enhance the performance of non-volatile memory technologies. The realization of the full potential of Al1-xScxN requires a comprehensive understanding of the mechanism of polarization reversal and domain structure dynamics involved in the ferroelectric switching process. In this work, transient current integration measurements performed by a pulse switching method are combined with domain imaging by piezoresponse force microscopy (PFM) to investigate the kinetics of domain nucleation and wall motion during polarization reversal in Al0.85Sc0.15N capacitors. In the studied electric field range (from 4.4 to 5.6 MV cm-1), ferroelectric switching proceeds via domain nucleation and wall movement. The currently available phenomenological models are shown to not fully capture all the details of the complex dynamics of polarization reversal in Al0.85Sc0.15N. PFM reveals a non-linear increase of both domain nucleation rate and lateral wall velocity during the switching process, as well as the dependency of the domain pattern on the polarization reversal direction. A continuously faster N- to M-polar switching upon cycling is reported and ascribed to an increasing number of M-polar nucleation sites and density of domain walls.

Scalable, accessible, and reproducible reference genome assembly and evaluation in Galaxy.

Improvements in genome sequencing and assembly are enabling high-quality reference genomes for all species. However, the assembly process is still laborious, computationally and technically demanding, lacks standards for reproducibility, and is not readily scalable. Here we present the latest Vertebrate Genomes Project assembly pipeline and demonstrate that it delivers high-quality reference genomes at scale across a set of vertebrate species arising over the last ~500 million years. The pipeline is versatile and combines PacBio HiFi long-reads and Hi-C-based haplotype phasing in a new graph-based paradigm. Standardized quality control is performed automatically to troubleshoot assembly issues and assess biological complexities. We make the pipeline freely accessible through Galaxy, accommodating researchers even without local computational resources and enhanced reproducibility by democratizing the training and assembly process. We demonstrate the flexibility and reliability of the pipeline by assembling reference genomes for 51 vertebrate species from major taxonomic groups (fish, amphibians, reptiles, birds, and mammals).

Role of Defects in the Breakdown Phenomenon of Al1-xScxN: From Ferroelectric to Filamentary Resistive Switching.

Aluminum scandium nitride (Al1-xScxN), with its large remanent polarization, is an attractive material for high-density ferroelectric random-access memories. However, the cycling endurance of Al1-xScxN ferroelectric capacitors is far below what can be achieved in other ferroelectric materials. Understanding the nature and dynamics of the breakdown mechanism is of the utmost importance for improving memory reliability. The breakdown phenomenon in ferroelectric Al1-xScxN is proposed to be an impulse thermal filamentary-driven process along preferential defective pathways. For the first time, stable and robust bipolar filamentary resistive switching in ferroelectric Al1-xScxN is reported. A hot atom damage defect generation model illustrates how filament formation and ferroelectric switching are connected. The model reveals the tendency of the ferroelectric wurtzite-type Al1-xScxN system to reach internal symmetry with bipolar electric field cycling. Defects generated from bipolar electric field cycling influence both the energy barrier between the polarization states and that required for the filament formation.

Genomics-driven breeding for local adaptation of durum wheat is enhanced by farmers' traditional knowledge.

In the smallholder, low-input farming systems widespread in sub-Saharan Africa, farmers select and propagate crop varieties based on their traditional knowledge and experience. A data-driven integration of their knowledge into breeding pipelines may support the sustainable intensification of local farming. Here, we combine genomics with participatory research to tap into traditional knowledge in smallholder farming systems, using durum wheat (Triticum durum Desf.) in Ethiopia as a case study. We developed and genotyped a large multiparental population, called the Ethiopian NAM (EtNAM), that recombines an elite international breeding line with Ethiopian traditional varieties maintained by local farmers. A total of 1,200 EtNAM lines were evaluated for agronomic performance and farmers' appreciation in three locations in Ethiopia, finding that women and men farmers could skillfully identify the worth of wheat genotypes and their potential for local adaptation. We then trained a genomic selection (GS) model using farmer appreciation scores and found that its prediction accuracy over grain yield (GY) was higher than that of a benchmark GS model trained on GY. Finally, we used forward genetics approaches to identify marker-trait associations for agronomic traits and farmer appreciation scores. We produced genetic maps for individual EtNAM families and used them to support the characterization of genomic loci of breeding relevance with pleiotropic effects on phenology, yield, and farmer preference. Our data show that farmers' traditional knowledge can be integrated in genomics-driven breeding to support the selection of best allelic combinations for local adaptation.

Thermal Stability of the Ferroelectric Properties in 100 nm-Thick Al0.72Sc0.28N.

The discovery of ferroelectricity in aluminum scandium nitride (Al1-xScxN) opens technological perspectives for harsh environments and space-related memory applications, considering the high-temperature stability of piezoelectricity in aluminum nitride. The ferroelectric and material properties of 100 nm-thick Al0.72Sc0.28N are studied up to 873 K, combining both electrical and in situ X-ray diffraction measurements as well as transmission electron microscopy and energy-dispersive X-ray spectroscopy. The present work demonstrates that Al0.72Sc0.28N can achieve high switching polarization and tunable coercive fields in a 375 K temperature range from room temperature up to 673 K. The degradation of the ferroelectric properties in the capacitors is observed above this temperature. Reduction of the effective top electrode area and consequent oxidation of the Al0.72Sc0.28N film are mainly responsible for this degradation. A slight variation of the Sc concentration is quantified across grain boundaries, even though its impact on the ferroelectric properties cannot be isolated from those brought by the top electrode deterioration and Al0.72Sc0.28N oxidation. The Curie temperature of Al0.72Sc0.28N is confirmed to be above 873 K, thus corroborating the promising thermal stability of this ferroelectric material. The present results further support the future adoption of Al1-xScxN in memory technologies for harsh environments like applications in space missions.

The Mitogenome Relationships and Phylogeography of Barn Swallows (Hirundo rustica).

The barn swallow (Hirundo rustica) poses a number of fascinating scientific questions, including the taxonomic status of postulated subspecies. Here, we obtained and assessed the sequence variation of 411 complete mitogenomes, mainly from the European H. r. rustica, but other subspecies as well. In almost every case, we observed subspecies-specific haplogroups, which we employed together with estimated radiation times to postulate a model for the geographical and temporal worldwide spread of the species. The female barn swallow carrying the Hirundo rustica ancestral mitogenome left Africa (or its vicinity) around 280 thousand years ago (kya), and her descendants expanded first into Eurasia and then, at least 51 kya, into the Americas, from where a relatively recent (<20 kya) back migration to Asia took place. The exception to the haplogroup subspecies specificity is represented by the sedentary Levantine H. r. transitiva that extensively shares haplogroup A with the migratory European H. r. rustica and, to a lesser extent, haplogroup B with the Egyptian H. r. savignii. Our data indicate that rustica and transitiva most likely derive from a sedentary Levantine population source that split at the end of the Younger Dryas (YD) (11.7 kya). Since then, however, transitiva received genetic inputs from and admixed with both the closely related rustica and the adjacent savignii. Demographic analyses confirm this species' strong link with climate fluctuations and human activities making it an excellent indicator for monitoring and assessing the impact of current global changes on wildlife.

Phosphorylation of H3-Thr3 by Haspin Is Required for Primary Cilia Regulation.

Primary cilia are commonly found on most quiescent, terminally differentiated cells and play a major role in the regulation of the cell cycle, cell motility, sensing, and cell-cell communication. Alterations in ciliogenesis and cilia maintenance are causative of several human diseases, collectively known as ciliopathies. A key determinant of primary cilia is the histone deacetylase HDAC6, which regulates their length and resorption and whose distribution is regulated by the death inducer-obliterator 3 (Dido3). Here, we report that the atypical protein kinase Haspin is a key regulator of cilia dynamics. Cells defective in Haspin activity exhibit longer primary cilia and a strong delay in cilia resorption upon cell cycle reentry. We show that Haspin is active in quiescent cells, where it phosphorylates threonine 3 of histone H3, a known mitotic Haspin substrate. Forcing Dido3 detachment from the chromatin prevents Haspin inhibition from impacting cilia dynamics, suggesting that Haspin activity is required for the relocalization of Dido3-HDAC6 to the basal body. Exploiting the zebrafish model, we confirmed the physiological relevance of this mechanism. Our observations shed light on a novel player, Haspin, in the mechanisms that govern the determination of cilia length and the homeostasis of mature cilia.

The genome sequence of the European nightjar, Caprimulgus europaeus (Linnaeus, 1758).

We present a genome assembly from an individual female Caprimulgus europaeus (the European nightjar; Chordata; Aves; Caprimulgiformes; Caprimulgidae). The genome sequence is 1,178 megabases in span. The majority of the assembly (99.33%) is scaffolded into 37 chromosomal pseudomolecules, including the W and Z sex chromosomes.

Haspin regulates Ras localization to promote Cdc24-driven mitotic depolarization.

Cell polarization is of paramount importance for proliferation, differentiation, development, and it is altered during carcinogenesis. Polarization is a reversible process controlled by positive and negative feedback loops. How polarized factors are redistributed is not fully understood and is the focus of this work. In Saccharomyces cerevisiae, mutants defective in haspin kinase exhibit stably polarized landmarks and are sensitive to mitotic delays. Here, we report a new critical role for haspin in polarisome dispersion; failure to redistribute polarity factors, in turn, leads to nuclear segregation defects and cell lethality. We identified a mitotic role for GTP-Ras in regulating the local activation of the Cdc42 GTPase, resulting in its dispersal from the bud tip to a homogeneous distribution over the plasma membrane. GTP-Ras2 physically interacts with Cdc24 regulateing its mitotic distribution. Haspin is shown to promote a mitotic shift from a bud tip-favored to a homogenous PM fusion of Ras-containing vesicles. In absence of haspin, active Ras is not redistributed from the bud tip; Cdc24 remains hyperpolarized promoting the activity of Cdc42 at the bud tip, and the polarisome fails to disperse leading to erroneously positioned mitotic spindle, defective nuclear segregation, and cell death after mitotic delays. These findings describe new functions for key factors that modulate cell polarization and mitotic events, critical processes involved in development and tumorigenesis.

Long walk to genomics: History and current approaches to genome sequencing and assembly.

Genomes represent the starting point of genetic studies. Since the discovery of DNA structure, scientists have devoted great efforts to determine their sequence in an exact way. In this review we provide a comprehensive historical background of the improvements in DNA sequencing technologies that have accompanied the major milestones in genome sequencing and assembly, ranging from early sequencing methods to Next-Generation Sequencing platforms. We then focus on the advantages and challenges of the current technologies and approaches, collectively known as Third Generation Sequencing. As these technical advancements have been accompanied by progress in analytical methods, we also review the bioinformatic tools currently employed in de novo genome assembly, as well as some applications of Third Generation Sequencing technologies and high-quality reference genomes.

ADAP2 in heart development: a candidate gene for the occurrence of cardiovascular malformations in NF1 microdeletion syndrome.

BACKGROUND: Cardiovascular malformations have a higher incidence in patients with NF1 microdeletion syndrome compared to NF1 patients with intragenic mutation, presumably owing to haploinsufficiency of one or more genes included in the deletion interval and involved in heart development. In order to identify which genes could be responsible for cardiovascular malformations in the deleted patients, we carried out expression studies in mouse embryos and functional studies in zebrafish. METHODS AND RESULTS: The expression analysis of three candidate genes included in the NF1 deletion interval, ADAP2, SUZ12 and UTP6, performed by in situ hybridisation, showed the expression of ADAP2 murine ortholog in heart during fundamental phases of cardiac morphogenesis. In order to investigate the role of ADAP2 in cardiac development, we performed loss-of-function experiments of zebrafish ADAP2 ortholog, adap2, by injecting two different morpholino oligos (adap2-MO and UTR-adap2-MO). adap2-MOs-injected embryos (morphants) displayed in vivo circulatory and heart shape defects. The molecular characterisation of morphants with cardiac specific markers showed that the injection of adap2-MOs causes defects in heart jogging and looping. Additionally, morphological and molecular analysis of adap2 morphants demonstrated that the loss of adap2 function leads to defective valvulogenesis, suggesting a correlation between ADAP2 haploinsufficiency and the occurrence of valve defects in NF1-microdeleted patients. CONCLUSIONS: Overall, our findings indicate that ADAP2 has a role in heart development, and might be a reliable candidate gene for the occurrence of cardiovascular malformations in patients with NF1 microdeletion and, more generally, for the occurrence of a subset of congenital heart defects.

Transverse craniofacial features and their genetic predisposition in families with nonsyndromic unilateral cleft lip and palate.

OBJECTIVE: The purpose of this study was to evaluate the transverse craniofacial form in families with nonsyndromic cleft lip and palate (NSCLP). It was hypothesized that affected as well as noncleft NSCLP family members are characterized by a common array of craniofacial features that differ from the general population. DESIGN: This was a prospective cross-sectional investigation that included affected children with NSCLP and their noncleft parents and siblings. PATIENTS, PARTICIPANTS: A total of 114 subjects (14 affected girls, 17 affected girls, 15 unaffected male siblings, 10 unaffected female siblings, 29 unaffected biological mothers, and 29 unaffected biological fathers) were included. Subject records comprised of posteroanterior cephalometric radiographs obtained from all 114 subjects. MAIN OUTCOME MEASURES: The width of midfacial structures, including the orbit and nose, was increased in NSCLP families, compared with published norms. Interestingly, the face was disproportionally wider in relation to total facial height. The transverse craniofacial form of children with or without clefts significantly correlated with that of their parents. Mothers displayed strong correlation with their affected and unaffected sons, whereas fathers correlated to their daughters, suggesting a possible sex-linked developmental influence. CONCLUSION: Better understanding of the genetic inheritance of craniofacial features associated with cleft lip and palate may ultimately contribute to the development of cleft risk assessment methods.

Association of nasomaxillary asymmetry in children with unilateral cleft lip and palate and their parents.

OBJECTIVE: It has been suggested previously that increased width of midfacial structures is associated with the development of palatal clefting. The aim of this study was to evaluate the association of transverse craniofacial asymmetry between children with unilateral cleft lip and palate (UCLP) and their parents. Specifically, we hypothesized that parental transverse craniofacial asymmetry is a risk factor associated with the development of asymmetry in children with UCLP. DESIGN: Retrospective cross-sectional investigation including affected children and their noncleft parents. PATIENTS, PARTICIPANTS: A total of 64 children-parent sets of data (32 child-biological mother + 32 child-biological father) were included. Subject records included posteroanterior cephalometric radiographs obtained from 29 Costa Rican families with UCLP. MAIN OUTCOME MEASURES: The side of parental nasal asymmetry was significantly associated with the side of cleft in their children. For the majority of parents with children suffering from a left cleft, nasal width was larger on the left, compared with the right side. Similarly, in the majority of parents with children suffering from a right cleft, nasal width was larger on the right, compared with the left side. CONCLUSION: The results suggest that unilaterally increased nasomaxillary width in parents may play a key role in the development of ipsilateral palatal clefting in their offspring, therefore underscoring the importance of craniofacial form as a genetic etiologic factor in the genesis of clefting. Better understanding of the role of craniofacial form in cleft development will ultimately allow for the assessment of risk for cleft lip and palate.

Association of distinct craniofacial features in nonsyndromic cleft lip and palate family members.

OBJECTIVE: To assess the relationship of distinct craniofacial features among family members with cleft lip and palate (CLP). METHODS: Lateral cephalometric and anthropometric measurements of the members of 28 Costa Rican families with CLP were analyzed. The distinct craniofacial features in subjects with CLP were identified by comparing their craniofacial measurements with published normative values. The presence of these features was assessed in the unaffected family members. Regression coefficients were computed to evaluate the association of the distinct craniofacial measurements between parents and their offspring with and without CLP. RESULTS: The male and female subjects with CLP were characterized by shortened head (HL), anterior cranial base (S-N), and palatal length (ANS-PNS, A-PNS) measurements as well as hyperdivergent angle of S-N plane to palatal plane (

Agenesia nasal / Nasal agenesia

Se presenta un caso de agenesia nasal, malformación congénita de rara ocurrencia y de incidencia desconocida que constituye un verdadero reto para el especialista que se enfrenta a ella por las implicaciones estéticas y funcionales que representa. Puede asociarse a otras malformaciones congénitas y en determinados casos poner en peligro la vida del recién nacido al presentar imposibilidad para respirar y comer de manera simultánea. Su manejo implica un grupo interdisciplinario y varias etapas quirúrgicas para un mejor resultado