The homeodomain protein PAL-1 specifies a lineage-specific regulatory network in the C. elegans embryo

Maternal and zygotic activities of the homeodomain protein PAL-1 specify the identity and maintain the development of the multipotent C blastomere lineage in the C. elegans embryo. To identify PAL-1 regulatory target genes, we used microarrays to compare transcript abundance in wild-type embryos with mutant embryos lacking a C blastomere and to mutant embryos with extra C blastomeres. pal-1-dependent C-lineage expression was verified for select candidate target genes by reporter gene analysis, though many of the target genes are expressed in additional lineages as well. The set of validated target genes includes 12 transcription factors, an uncharacterized wingless ligand and five uncharacterized genes. Phenotypic analysis demonstrates that the identified PAL-1 target genes affect specification, differentiation and morphogenesis of C-lineage cells. In particular, we show that cell fate-specific genes (or tissue identity genes) and a posterior HOX gene are activated in lineage-specific fashion. Transcription of targets is initiated in four temporal phases, which together with their spatial expression patterns leads to a model of the regulatory network specified by PAL-1

Synthetic lethal analysis of Caenorhabditis elegans posterior embryonic patterning genes identifies conserved genetic interactions

Phenotypic robustness is evidenced when single-gene mutations do not result in an obvious phenotype. It has been suggested that such phenotypic stability results from 'buffering' activities of homologous genes as well as non-homologous genes acting in parallel pathways. One approach to characterizing mechanisms of phenotypic robustness is to identify genetic interactions, specifically, double mutants where buffering is compromised. To identify interactions among genes implicated in posterior patterning of the Caenorhabditis elegans embryo, we measured synthetic lethality following RNA interference of 22 genes in 15 mutant strains. A pair of homologous T-box transcription factors (tbx-8 and tbx-9) is found to interact in both C. elegans and C. briggsae, indicating that their compensatory function is conserved. Furthermore, a muscle module is defined by transitive interactions between the MyoD homolog hlh-1, another basic helix-loop-helix transcription factor, hnd-1, and the MADS-box transcription factor unc-120. Genetic interactions within a homologous set of genes involved in vertebrate myogenesis indicate broad conservation of the muscle module and suggest that other genetic modules identified in C. elegans will be conserved

Presynchronizing PGF2α and GnRH injections before timed artificial insemination CO-Synch + CIDR program

Fixed-time artificial insemination is an effective management tool that reduces the labor associated with more conventional artificial insemination programs requiring detection of estrus. The 7-day CO-Synch + controlled internal drug release (CIDR) insert protocol has been shown to effectively initiate estrus and ovulation in cycling and non-cycling suckled beef cows, producing pregnancy rates at or greater than 50% in beef cows. The gonadotropin-releasing hormone (GnRH) injection that begins the CO-Synch + CIDR program initiates ovulation in a large proportion of cows, particularly anestrous cows. The CIDR, which releases progesterone intravaginally, prevents short estrous cycles that usually follow the first postpartum ovulation in beef cows. Our hypothesis was that inducing estrus with a prostaglandin injection followed 3 days later with a GnRH injection, 7 days before applying the 7-day CO-Synch + CIDR protocol, might increase the percentage of cycling cows that would exhibit synchronous follicular waves after the onset of the CO-Synch + CIDR protocol. We also hypothesized that the additional GnRH injection would increase the percentage of anestrous cows that would ovulate, thereby increasing pregnancy outcomes

Accessibility and applicability of currently available e-mental health programs for depression for people with poststroke aphasia: Scoping review

© Stephanie Jane Clunne, Brooke Jade Ryan, Annie Jane Hill, Caitlin Brandenburg, Ian Kneebone. Background: Depression affects approximately 60% of people with aphasia 1 year post stroke and is associated with disability, lower quality of life, and mortality. Web-delivered mental health (e-mental health) programs are effective, convenient, and cost-effective for the general population and thus are increasingly used in the management of depression. However, it is unknown if such services are applicable and communicatively accessible to people with poststroke aphasia. Objective: The aim of this study was to identify freely available e-mental health programs for depression and determine their applicability and accessibility for people with poststroke aphasia. Methods: A Web-based search was conducted to identify and review freely available e-mental health programs for depression. These programs were then evaluated in terms of their (1) general features via a general evaluation tool, (2) communicative accessibility for people with aphasia via an aphasia-specific communicative accessibility evaluation tool, and (3) empirical evidence for the general population and stroke survivors with and without aphasia. The program that met the most general evaluation criteria and aphasia-specific communicative accessibility evaluation criteria was then trialed by a small subgroup of people with poststroke aphasia. Results: A total of 8 programs were identified. Of these, 4 had published evidence in support of their efficacy for use within the general population. However, no empirical evidence was identified that specifically supported any programs’ use for stroke survivors with or without aphasia. One evidence-based program scored at least 80% (16/19 and 16/20, respectively) on both the general and aphasia-specific communicative accessibility evaluation tools and was subject to a preliminary trial by 3 people with poststroke aphasia. During this trial, participants were either unable to independently use the program or gave it low usability scores on a post-trial satisfaction survey. On this basis, further evaluation was considered unwarranted. Conclusions: Despite fulfilling majority of the general evaluation and aphasia-specific evaluation criteria, the highest rated program was still found to be unsuitable for people with poststroke aphasia. Thus, e-mental health programs require substantial redevelopment if they are likely to be useful to people with poststroke aphasia

A unified mechanism for intron and exon definition and back-splicing.

The molecular mechanisms of exon definition and back-splicing are fundamental unanswered questions in pre-mRNA splicing. Here we report cryo-electron microscopy structures of the yeast spliceosomal E complex assembled on introns, providing a view of the earliest event in the splicing cycle that commits pre-mRNAs to splicing. The E complex architecture suggests that the same spliceosome can assemble across an exon, and that it either remodels to span an intron for canonical linear splicing (typically on short exons) or catalyses back-splicing to generate circular RNA (on long exons). The model is supported by our experiments, which show that an E complex assembled on the middle exon of yeast EFM5 or HMRA1 can be chased into circular RNA when the exon is sufficiently long. This simple model unifies intron definition, exon definition, and back-splicing through the same spliceosome in all eukaryotes and should inspire experiments in many other systems to understand the mechanism and regulation of these processes

Surface effects on the orbital order in the single layered manganite La0.5Sr1.5MnO4

We report the first observation of `orbital truncation rods' -- the scattering arising from the termination of bulk orbital order at the surface of a crystal. The x-ray measurements, performed on a cleaved, single-layered perovskite, La0.5Sr1.5MnO4, reveal that while the crystallographic surface is atomically smooth, the orbital `surface' is much rougher, with an r.m.s. deviation from the average `surface' of ~0.7nm. The temperature dependence of this scattering shows evidence of a surface-induced second order transition.Comment: 13 pages, 4 figure

Un couple fantomatique : le conte et la fable chez quelques fabulistes des Lumières

Si les fabulistes des Lumières déploient un important appareil théorique pour s’efforcer de donner au petit genre qu’ils pratiquent une poétique — tirée de l’analyse de l’œuvre de La Fontaine ou issue d’une reformulation des préceptes de la tradition didactique et rhétorique —, ils semblent n’avoir guère réfléchi sur l’articulation entre fable et conte, même dans les cas, assez nombreux, où les deux termes figurent au titre de leurs recueils : les étiquettes paraissent interchangeables et les discours liminaires comme les apologues confirment une adhésion non problématique à la définition, souvent répétée, de La Fontaine selon laquelle une fable doit être « un conte » destiné à faire passer « le précepte avec lui ». Seules les Fables nouvelles de l’abbé Aubert, dans leur édition de 1773, esquissent — sans la théoriser — une distinction entre fable et conte, en choisissant une structure originale pour le recueil : symétriquement dans chacune des deux parties, les livres de fables (à l’exception des livres conclusifs, dotés d’un simple « épilogue ») sont terminés par un « conte moral », ce qui souligne l’inflexion de l’ouvrage, à l’origine dominé par les thématiques religieuses ou politiques, vers un moralisme domestique et sensible.If the fabulists of the Enlightenment display an important theoretical apparatus to try and give a poetics to the fable—that is derived from La Fontaine or from a reformulation of the tenets of the didactic and rhetorical tradition—, they do not seem to have considered the relationship between fable and tale, even when both appear in the titles of their books. Labels seem interchangeable and prefatory discourses as well as the apologues confirm an unproblematic adhesion to La Fontaine’s often repeated definition of a fable that must be “a tale” intended to raise “the precept with it”. Only the Fables nouvelles of Abbé Aubert in their edition of 1773 outline (without theorizing it) a distinction between fable and tale by choosing an original structure for the collection: symmetrically in both parties, books of fables (except conclusive books, with a simple “epilogue”) are terminated by a “moral tale”, which underlines the shift in the tale in which the originally religious or political themes gradually turn into a domestic and sensible moralism

Exclusive semileptonic Bs→KℓνB_s\to K \ell \nu decays on the lattice

Semileptonic $B_s \to K \ell \nu$ decays provide an alternative $b$-decay channel to determine the CKM matrix element $|V_{ub}|$, and to obtain a $R$-ratio to investigate lepton-flavor-universality violations. Results for the CKM matrix element may also shed light on the discrepancies seen between analyses of inclusive or exclusive decays. We calculate the decay form factors using lattice QCD with domain-wall light quarks and a relativistic $b$-quark. We analyze data at three lattice spacings with unitary pion masses down to $268\,\mathrm{MeV}$. Our numerical results are interpolated/extrapolated to physical quark masses and to the continuum to obtain the vector and scalar form factors $f_+(q^2)$ and $f_0(q^2)$ with full error budgets at $q^2$ values spanning the range accessible in our simulations. We provide a possible explanation of tensions found between results for the form factor from different lattice collaborations. Model- and truncation-independent $z$-parameterization fits following a recently proposed Bayesian-inference approach extend our results to the entire allowed kinematic range. Our results can be combined with experimental measurements of $B_s \to D_s$ and $B_s\to K$ semileptonic decays to determine $|V_{ub}|=3.8(6)\times 10^{-3}$. The error is currently dominated by experiment. We compute differential branching fractions and two types of $R$ ratios, the one commonly used as well as a variant better suited to test lepton-flavor universality.Comment: Version accepted and published (Phys. Rev. D 107, 114512) 30 pages, 13 Figures, supplementary data fil