Explore the vast range of titles available.

As Kate Pearson on the television show This Is Us, Metz presents a character that viewers see themselves in, no matter what they look like or where they come from. Now she shares her story, and shows how she has applied the lessons she learned from both setbacks and successes. She offers practical applications of her insights, blending love and experience. Metz encourages us all to claim our rightful place in a world that may be trying to knock us down, find our own unique gifts, and pursue our dreams.

Background Early stages of fruit development from initial set through exponential growth are critical determinants of size and yield, however, there has been little detailed analysis of this phase of development. In this study we combined morphological analysis with 454 pyrosequencing to study transcript level changes occurring in young cucumber fruit at five ages from anthesis through the end of exponential growth. Results The fruit samples produced 1.13 million ESTs which were assembled into 27,859 contigs with a mean length of 834 base pairs and a mean of 67 reads per contig. All contigs were mapped to the cucumber genome. Principal component analysis separated the fruit ages into three groups corresponding with cell division/pre-exponential growth (0 and 4 days post pollination (dpp)), peak exponential expansion (8dpp), and late/post-exponential expansion stages of growth (12 and 16 dpp). Transcripts predominantly expressed at 0 and 4 dpp included homologs of histones, cyclins, and plastid and photosynthesis related genes. The group of genes with peak transcript levels at 8dpp included cytoskeleton, cell wall, lipid metabolism and phloem related proteins. This group was also dominated by genes with unknown function or without known homologs outside of cucurbits. A second shift in transcript profile was observed at 12-16dpp, which was characterized by abiotic and biotic stress related genes and significant enrichment for transcription factor gene homologs, including many associated with stress response and development. Conclusions The transcriptome data coupled with morphological analyses provide an informative picture of early fruit development. Progressive waves of transcript abundance were associated with cell division, development of photosynthetic capacity, cell expansion and fruit growth, phloem activity, protection of the fruit surface, and finally transition away from fruit growth toward a stage of enhanced stress responses. These results suggest that the interval between expansive growth and ripening includes further developmental differentiation with an emphasis on defense. The increased transcript levels of cucurbit-specific genes during the exponential growth stage may indicate unique factors contributing to rapid growth in cucurbits.

\"Young Steve Rogers is determined to do his part for the war effort--and despite his frail form, his strength of will makes him the ideal candidate for the Super-Soldier program. Newly transformed into Captain America, the Sentinel of Liberty, Steve becomes the face of freedom--but how will this newly minted hero react when he must face the Red Skull? Plus: all-new pulp adventures told in the classic newspaper-strip format! Cap and his sidekick, Bucky, serve up daily helpings of adventure filled with robots, secret underground cities, femme fatales and no-good Nazis just waiting for a sock in the jaw! It's two retro-inspired, classic-style World War II-era Cap Adventures for the price of one!\"--Page 4 of cover.

The substantial burden of post-COVID-19 condition (also known as long COVID) underscores the need for effective pharmacological interventions. Given that viral persistence has been hypothesised as a potential cause of long COVID, antiviral therapy might offer a promising approach to alleviating long COVID symptoms. We therefore investigated the efficacy, safety, and tolerability of nirmatrelvir–ritonavir for treating long COVID. In this phase 2, decentralised, double-blind, randomised controlled trial, adults (aged ≥18 years) from the 48 states across the contiguous USA, with previous documented SARS-CoV-2 infection and long COVID symptoms starting within 4 weeks of initial infection and persisting for at least 12 weeks, were eligible for inclusion. Key exclusion criteria were use of nirmatrelvir–ritonavir within the previous 2 months, CYP3A4-dependent medications, or strong CYP3A4 inducers; acute medical illness such as SARS-CoV-2 infection within the past 2 weeks; active liver disease; renal impairment; and immunocompromise. Using software for 1:1 stratified block random assignment, participants were randomly allocated to receive either two tablets of nirmatrelvir (150 mg each) and one tablet of ritonavir (100 mg), or placebo and one tablet of ritonavir (100 mg), orally administered twice daily for 15 days, stratified by age, sex at birth, and COVID-19 vaccination status. Participants, clinicians, and the study team were masked to treatment allocation. The primary efficacy endpoint was the change in the Patient-Reported Outcomes Measurement Information System (PROMIS)-29 Physical Health Summary Score (PHSS) from baseline to day 28, analysed by intention to treat. Safety endpoints were reported from baseline to week 6 in all participants who were exposed to the study treatment. This trial is registered with ClinicalTrials.gov (NCT05668091) and is now closed to new participants. Between April 14, 2023, and Feb 26, 2024, 119 participants were screened. 100 were enrolled (66 [66%] female participants and 34 [34%] male participants), with 49 assigned to the nirmatrelvir–ritonavir group and 51 to the placebo–ritonavir group (intention-to-treat population). Three participants in the nirmatrelvir–ritonavir group and two in the placebo–ritonavir group withdrew before starting treatment and were excluded from the safety population. The mean PROMIS-29 PHSS at baseline was 39·6 (95% CI 37·4 to 41·9) in the nirmatrelvir–ritonavir group and 36·3 (34·4 to 38·2) in the placebo–ritonavir group. The adjusted change from baseline to day 28 was 0·45 (–0·93 to 1·83) in the nirmatrelvir–ritonavir group and 1·01 (–0·30 to 2·31) in the placebo–ritonavir group (adjusted mean difference –0·55 [95% CI –2·32 to 1·21; p=0·54]). No deaths or serious adverse events were recorded between baseline and week 6. Study drug-related treatment-emergent adverse events were reported in more participants in the nirmatrelvir–ritonavir group (35 [76%] of 46) compared with the placebo–ritonavir group (27 [55%] of 49), mostly driven by dysgeusia. Early treatment termination due to an adverse event occurred in two participants in the nirmatrelvir–ritonavir group and one in the placebo–ritonavir group. Nirmatrelvir–ritonavir administered for 15 days did not significantly improve health outcomes in participants with long COVID compared with placebo–ritonavir at day 28. However, the study showed the feasibility of large-scale, decentralised trials in long COVID. Pfizer, Fred Cohen, and Carolyn Klebanoff.

Very young cucumber (Cucumis sativus) fruit are highly susceptible to infection by the oomycete pathogen, Phytophthora capsici. As the fruit complete exponential growth, at approximately 10-12 days post pollination (dpp), they transition to resistance. The development of age-related resistance (ARR) is increasingly recognized as an important defense against pathogens, however, underlying mechanisms are largely unknown. Peel sections from cucumber fruit harvested at 8 dpp (susceptible) and 16 dpp (resistant) showed equivalent responses to inoculation as did whole fruit, indicating that the fruit surface plays an important role in defense against P. capsici. Exocarp from 16 dpp fruit had thicker cuticles, and methanolic extracts of peel tissue inhibited growth of P. capsici in vitro, suggesting physical or chemical components to the ARR. Transcripts specifically expressed in the peel vs. pericarp showed functional differentiation. Transcripts predominantly expressed in the peel were consistent with fruit surface associated functions including photosynthesis, cuticle production, response to the environment, and defense. Peel-specific transcripts that exhibited increased expression in 16 dpp fruit relative to 8 dpp fruit, were highly enriched (P<0.0001) for response to stress, signal transduction, and extracellular and transport functions. Specific transcripts included genes associated with potential physical barriers (i.e., cuticle), chemical defenses (flavonoid biosynthesis), oxidative stress, penetration defense, and molecular pattern (MAMP)-triggered or effector-triggered (R-gene mediated) pathways. The developmentally regulated changes in gene expression between peels from susceptible- and resistant- age fruits suggest programming for increased defense as the organ reaches full size.

C₄ photosynthesis involves alterations to the biochemistry, cell biology, and development of leaves. Together, these modifications increase the efficiency of photosynthesis, and despite the apparent complexity of the pathway, it has evolved at least 45 times independently within the angiosperms. To provide insight into the extent to which gene expression is altered between C₃ and C₄ leaves, and to identify candidates associated with the C₄ pathway, we used massively parallel mRNA sequencing of closely related C₃ (Cleome spinosa) and C₄ (Cleome gynandra) species. Gene annotation was facilitated by the phylogenetic proximity of Cleome and Arabidopsis (Arabidopsis thaliana). Up to 603 transcripts differ in abundance between these C₃ and C₄ leaves. These include 17 transcription factors, putative transport proteins, as well as genes that in Arabidopsis are implicated in chloroplast movement and expansion, plasmodesmatal connectivity, and cell wall modification. These are all characteristics known to alter in a C₄ leaf but that previously had remained undefined at the molecular level. We also document large shifts in overall transcription profiles for selected functional classes. Our approach defines the extent to which transcript abundance in these C₃ and C₄ leaves differs, provides a blueprint for the NAD-malic enzyme C₄ pathway operating in a dicotyledon, and furthermore identifies potential regulators. We anticipate that comparative transcriptomics of closely related species will provide deep insight into the evolution of other complex traits.

Some microbial eukaryotes, such as the extremophilic red alga Galdieria sulphuraria, live in hot, toxic metal-rich, acidic environments. To elucidate the underlying molecular mechanisms of adaptation, we sequenced the 13.7-megabase genome of G. sulphuraria. This alga shows an enormous metabolic flexibility, growing either photoautotrophically or heterotrophically on more than 50 carbon sources. Environmental adaptation seems to have been facilitated by horizontal gene transfer from various bacteria and archaea, often followed by gene family expansion. At least 5% of protein-coding genes of G. sulphuraria were probably acquired horizontally. These proteins are involved in ecologically important processes ranging from heavy-metal detoxification to glycerol uptake and metabolism. Thus, our findings show that a pan-domain gene pool has facilitated environmental adaptation in this unicellular eukaryote.

Autism or autism spectrum disorder (ASD) is described as a lifelong condition with core behavioural symptoms appearing during infancy or early childhood. Genetic and other effects occurring during the earliest times of life are thought to play a significant contributory role to the presentation of autism, denoting that autism is typically seen as an innate or inborn condition. Such descriptions have, and continue to, define autism research and clinical practice. Inspection of the existing research literature, however, suggests that within the vast heterogeneity of autism, not everyone experiences autism in such a prescribed way. Various reports have observed the presentation of \"acquired autism\" following a period of typical development. Other findings have documented an abatement of clinically relevant autistic features and related comorbid pathology for some. Such reports offer important insights into the heterogeneity and complexity of autism. Keywords: autism, regression, innate, lifelong, acquired, heterogeneity

Free-floating thrombi of the common carotid artery (CCA) are a very rare cause of ischemic stroke. To date, only a few reports have been described in the academic literature. Revascularization is indicated due to the risk of thromboembolic disease and hemodynamic-related stroke syndromes. Medical treatment typically includes anticoagulation and, in some circumstances, open surgical thrombectomy is an additional option. Although rarely described in the literature, endovascular thrombectomy is a viable treatment alternative in these patients.