The onset of a major seagrass initiative in West Africa enabled important seagrass discoveries in several countries, in one of the least documented seagrass regions in the world. Four seagrass ...species occur in western Africa, Cymodocea nodosa, Halodule wrightii, Ruppia maritima and Zostera noltei. An area of about 62,108 ha of seagrasses was documented in the studied region comprising seven countries: Mauritania, Senegal, The Gambia, Guinea Bissau, Guinea, Sierra Leone and Cabo Verde. Extensive meadows of Zostera noltei were recorded for the first time at Saloum Delta, Senegal, which represents the new southernmost distribution limit of this species. This paper also describes the seagrass morphology for some study areas and explores the main stressors to seagrasses as well as conservation initiatives to protect these newly documented meadows in West Africa. The produced information and maps serve as a starting point for researchers and managers to monitor temporal and spatial changes in the meadows’ extent, health and condition as an efficient management tool.
The inability to purify and culture astrocytes has long hindered studies of their function. Whereas astrocyte progenitor cells can be cultured from neonatal brain, culture of mature astrocytes from ...postnatal brain has not been possible. Here, we report a new method to prospectively purify astrocytes by immunopanning. These astrocytes undergo apoptosis in culture, but vascular cells and HBEGF promote their survival in serum-free culture. We found that some developing astrocytes normally undergo apoptosis in vivo and that the vast majority of astrocytes contact blood vessels, suggesting that astrocytes are matched to blood vessels by competing for vascular-derived trophic factors such as HBEGF. Compared to traditional astrocyte cultures, the gene profiles of the cultured purified postnatal astrocytes much more closely resemble those of in vivo astrocytes. Although these astrocytes strongly promote synapse formation and function, they do not secrete glutamate in response to stimulation.
► Developed a novel method to purify and culture rat and mouse brain astrocytes ► Identified growth factors, vascular cells as needed for astrocyte survival in vitro ► Hypothesize that astrocytes are matched to blood vessels ► Showed that our culture system is a better representation of the in vivo astrocytes
This research addresses consumers' willingness-to-punish the corporate brand for corporate social irresponsibility (CSI). It is supported by the extant literature on consumer stakeholders, corporate ...brands, brand personality, regulatory fit, and psychological contract, as well as by punishment in psychology and philosophy, which are new to the marketing literature. Using an experimental design with a control group, this research examines consumers' willingness-to-reward and its converse willingness-to-punish a corporate brand under three treatment conditions of socially responsible, socially irresponsible, and environmentally friendly. Data were collected on four outcome variables of willingness-to-punish, willingness-to-reward, brand attitude, and purchase intention for each treatment group. MANOVA results indicated that there were systematic differences in the levels of outcomes among the four groups. Discriminant function analysis found the socially irresponsible group was statistically significantly different from the other three experimental groups for all four outcome variables. Consumers dealing with socially irresponsible corporate brands were more likely to punish and less likely to reward than consumers in the other three treatment conditions. This study illustrates the latent negative impact from CSI activities on four important dimensions of consumer response. The findings indicate there is a pragmatic need for corporate brand strategists to recognize consumers' willingness-to-punish the corporate brand and the subsequent necessity to avoid activities that consumers may perceive to be socially irresponsible.
Circadian rhythmicity and sleep homeostasis interact to regulate sleep-wake cycles
1–4, but the genetic basis of individual differences in sleep-wake regulation remains largely unknown
5.
PERIOD ...genes are thought to contribute to individual differences in sleep timing by affecting circadian rhythmicity
6, but not sleep homeostasis
7, 8. We quantified the contribution of a variable-number tandem-repeat polymorphism in the coding region of the circadian clock gene
PERIOD3 (
PER3)
9, 10 to sleep-wake regulation in a prospective study, in which 24 healthy participants were selected only on the basis of their
PER3 genotype. Homozygosity for the longer allele (
PER3
5/5
) had a considerable effect on sleep structure, including several markers of sleep homeostasis: slow-wave sleep (SWS) and electroencephalogram (EEG) slow-wave activity in non-rapid eye movement (non-REM) sleep and theta and alpha activity during wakefulness and REM sleep were all increased in
PER3
5/5
compared to
PER3
4/4
individuals. In addition, the decrement of cognitive performance in response to sleep loss was significantly greater in the
PER3
5/5
individuals. By contrast, the circadian rhythms of melatonin, cortisol, and peripheral
PER3 mRNA expression were not affected. The data show that this polymorphism in
PER3 predicts individual differences in the sleep-loss-induced decrement in performance and that this differential susceptibility may be mediated by its effects on sleep homeostasis.
STK11 and KEAP1 mutations (STK11 mutant STK11MUT and KEAP1MUT) are among the most often mutated genes in lung adenocarcinoma (LUAD). Although STK11MUT has been associated with resistance to ...programmed death-(ligand)1 (PD-L1) inhibition in KRASMUT LUAD, its impact on immunotherapy efficacy in KRAS wild-type (KRASWT) LUAD is currently unknown. Whether KEAP1MUT differentially affects outcomes to PD-(L)1 inhibition in KRASMUT and KRASWT LUAD is also unknown.
Clinicopathologic and genomic data were collected from September 2013 to September 2020 from patients with advanced LUAD at the Dana-Farber Cancer Institute/Massachusetts General Hospital cohort and the Memorial Sloan Kettering Cancer Center/MD Anderson Cancer Center cohort. Clinical outcomes to PD-(L)1 inhibition were analyzed according to KRAS, STK11, and KEAP1 mutation status in two independent cohorts. The Cancer Genome Atlas transcriptomic data were interrogated to identify differences in tumor gene expression and tumor immune cell subsets, respectively, according to KRAS/STK11 and KRAS/KEAP1 comutation status.
In the combined cohort (Dana-Farber Cancer Institute/Massachusetts General Hospital + Memorial Sloan Kettering Cancer Center/MD Anderson Cancer Center) of 1261 patients (median age = 61 y range: 22–92, 708 women 56.1%, 1065 smokers 84.4%), KRAS mutations were detected in 536 cases (42.5%), and deleterious STK11 and KEAP1 mutations were found in 20.6% (260 of 1261) and 19.2% (231 of 1202) of assessable cases, respectively. In each independent cohort and in the combined cohort, STK11 and KEAP1 mutations were associated with significantly worse progression-free (STK11 hazard ratio HR = 2.04, p < 0.0001; KEAP1 HR = 2.05, p < 0.0001) and overall (STK11 HR = 2.09, p < 0.0001; KEAP1 HR = 2.24, p < 0.0001) survival to immunotherapy uniquely among KRASMUT but not KRASWT LUADs. Gene expression ontology and immune cell enrichment analyses revealed that the presence of STK11 or KEAP1 mutations results in distinct immunophenotypes in KRASMUT, but not in KRASWT, lung cancers.
STK11 and KEAP1 mutations confer worse outcomes to immunotherapy among patients with KRASMUT but not among KRASWT LUAD. Tumors harboring concurrent KRAS/STK11 and KRAS/KEAP1 mutations display distinct immune profiles in terms of gene expression and immune cell infiltration.
A grading system for pulmonary adenocarcinoma has not been established. The International Association for the Study of Lung Cancer pathology panel evaluated a set of histologic criteria associated ...with prognosis aimed at establishing a grading system for invasive pulmonary adenocarcinoma.
A multi-institutional study involving multiple cohorts of invasive pulmonary adenocarcinomas was conducted. A cohort of 284 stage I pulmonary adenocarcinomas was used as a training set to identify histologic features associated with patient outcomes (recurrence-free survival RFS and overall survival OS). Receiver operating characteristic curve analysis was used to select the best model, which was validated (n = 212) and tested (n = 300, including stage I–III) in independent cohorts. Reproducibility of the model was assessed using kappa statistics.
The best model (area under the receiver operating characteristic curve AUC = 0.749 for RFS and 0.787 for OS) was composed of a combination of predominant plus high-grade histologic pattern with a cutoff of 20% for the latter. The model consists of the following: grade 1, lepidic predominant tumor; grade 2, acinar or papillary predominant tumor, both with no or less than 20% of high-grade patterns; and grade 3, any tumor with 20% or more of high-grade patterns (solid, micropapillary, or complex gland). Similar results were seen in the validation (AUC = 0.732 for RFS and 0.787 for OS) and test cohorts (AUC = 0.690 for RFS and 0.743 for OS), confirming the predictive value of the model. Interobserver reproducibility revealed good agreement (k = 0.617).
A grading system based on the predominant and high-grade patterns is practical and prognostic for invasive pulmonary adenocarcinoma.
This overview of the fifth edition of the WHO classification of thymic epithelial tumors (including thymomas, thymic carcinomas, and thymic neuroendocrine tumors NETs), mediastinal germ cell tumors, ...and mesenchymal neoplasms aims to (1) list established and new tumor entities and subtypes and (2) focus on diagnostic, molecular, and conceptual advances since publication of the fourth edition in 2015. Diagnostic advances are best exemplified by the immunohistochemical characterization of adenocarcinomas and the recognition of genetic translocations in metaplastic thymomas, rare B2 and B3 thymomas, and hyalinizing clear cell carcinomas. Advancements at the molecular and tumor biological levels of utmost oncological relevance are the findings that thymomas and most thymic carcinomas lack currently targetable mutations, have an extraordinarily low tumor mutational burden, but typically have a programmed death-ligand 1high phenotype. Finally, data underpinning a conceptual advance are illustrated for the future classification of thymic NETs that may fit into the classification scheme of extrathoracic NETs. Endowed with updated clinical information and state-of-the-art positron emission tomography and computed tomography images, the fifth edition of the WHO classification of thymic epithelial tumors, germ cell tumors, and mesenchymal neoplasms with its wealth of new diagnostic and molecular insights will be a valuable source for pathologists, radiologists, surgeons, and oncologists alike. Therapeutic perspectives and research challenges will be addressed as well.
Economic stability is dependent on the effective functioning and resilience of energy systems. Resilience is a term used across all research disciplines and in everyday discourse. As a concept it ...purports to serve as a useful indicator of sustainability and robustness, but it has proved difficult to measure. Ecological resilience, psychological resilience, risk management and energy security are all fields of research in which measures of the ability to respond to the unexpected are sought. The goal is to build adaptive capacity but quite different methods have been developed to achieve this end. Research on energy security, in particular, has focused on the security of oil supplies, not resilience or the adaptive capacity of the energy system or the role that renewable energy plays in building such capacity. This paper discusses how different disciplines seek to measure and build resilience and explores its connection with the state or quality of a system’s adaptive capacity. When the parameters of redundancy and diversity are present, resilience is enhanced. For this reason, in energy systems we must understand the size and scope of the key parameters required to facilitate the development of adaptive capacity and to build resilience that can enhance economic stability.
Metaplastic thymomas are rare biphasic thymic tumors that are characteristically well-circumscribed, confined to the thymus, and follow a benign to indolent clinical course. Their relationship to ...other thymic neoplasms remains unclear, and their molecular characteristics have not been defined. We report for the first time recurrent translocation events in metaplastic thymomas involving the Yes Associated Protein 1 (YAP1) and Mastermind Like Transcriptional Coactivator 2 (MAML2) genes. Eight metaplastic thymomas were retrieved from two institutions' archives over a 21-year period. Paraffin-embedded material from all cases underwent targeted DNA-based hybrid capture next-generation sequencing. Cases showing no somatic alterations subsequently underwent targeted RNA sequencing. Allele-specific real-time polymerase chain reaction was performed to detect GTF2I c.74146970T>A (p.L424H) mutations. All cases showed characteristic histologic features of metaplastic thymoma and demonstrated no local recurrence or distant metastatic disease at 1-22 years of follow-up. Six of eight cases were successfully sequenced, all showing YAP1-MAML2 fusions; in four cases the fusions were detected by DNA sequencing and in two cases by RNA sequencing. Two distinct products were identified: 5' YAP1 exon 1 fused to 3' MAML2 exons 2-5 or 5' YAP1 exons 1-5 fused to 3' MAML2 exons 2-5. All cases underwent allele-specific real-time polymerase chain reaction and demonstrated no GTF2I L424H mutations. Metaplastic thymoma is a distinct, clinically indolent thymic epithelial neoplasm characterized by YAP1-MAML2 fusion and lacking the GTF2I mutations found in Type A and AB thymomas.
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