Miracle-dz/UniFAR-FTUs huggingface dataset:
Influence of light and temperature on Prochlorococcus ecotype distributions in the Atlantic Ocean

In a focused analysis of Prochlorococcus population structure in the western North Atlantic, we found that the relative abundances of ecotypes varied significantly with depth and, at seasonally stratified locations, with degree of vertical mixing. More limited regional variation was observed (e.g., Sargasso Sea, Gulf Stream, continental slope, and equatorial current), and local patchiness was minimal. Modeling of a combined North and South Atlantic data set revealed significant, independent effects of light and temperature on ecotype abundances, suggesting that they are key ecological determinants that establish the different habitat ranges of the physiologically and genetically distinct ecotypes. This was in sharp contrast with the genus Synechococcus, whose total abundance was related to light but did not vary in a predictable way with temperature. Comparisons of field abundances with growth characteristics of cultured isolates of Prochlorococcus suggested the presence of ecotypespecific thermal and light adaptations that could be responsible for the distinct distribution patterns of the four dominant ecotypes. Significantly, we discovered that one “low‐light‐adapted” ecotype, eNATL2A, can thrive in deeply mixed surface layers, whereas another, eMIT9313, cannot, even though they have the same growth optimum for (low) light.
Dietary Phytase and Lactic Acid-Treated Cereal Grains Differently Affected Calcium and Phosphorus Homeostasis from Intestinal Uptake to Systemic Metabolism in a Pig Model

High intestinal availability of dietary phosphorus (P) may impair calcium (Ca) homeostasis and bone integrity. In the present study, we investigated the effect of phytase supplementation in comparison to the soaking of cereal grains in 2.5% lactic acid (LA) on intestinal Ca and P absorption; intestinal, renal, and bone gene expression regarding Ca and P homeostasis; bone parameters; and serum levels of regulatory hormones in growing pigs. Thirty-two pigs were randomly assigned to one of four diets in a 2 × 2 factorial design in four replicate batches for 19 days. The diets comprised either untreated or LA-treated wheat and maize without and with phytase supplementation (500 phytase units/kg). Although both treatments improved the P balance, phytase and LA-treated cereals differently modulated gene expression related to intestinal absorption, and renal and bone metabolism of Ca and P, thereby altering homeostatic regulatory mechanisms as indicated by serum Ca, P, vitamin D, and fibroblast growth factor 23 levels. Moreover, phytase increased the gene expression related to reabsorption of Ca in the kidney, whereas LA-treated cereals decreased the expression of genes for osteoclastogenesis in bones, indicating an unbalanced systemic availability of minerals. In conclusion, high intestinal availability of dietary P may impair Ca homeostasis and bone integrity.
The Statistical Theory of Pollen Analysis

This paper represents an attempt to apply statistical analysis to the method of counting fossil pollen, in the hope of justifying or disqualifying the validity of the present method of pollen analysis. Inasmuch as the question frequently arises as to the validity of the method of sampling (i.e. the analysis of the sample represented on a slide), it seems timely that a statistical study of this method be made. The purpose of present studies of peat pollens is to obtain indicators of past climates. In general when one finds a stratum containing a high percentage of pollen characteristic of any type of climate, it is concluded that that type of climate existed during the deposition of the stratum; where one finds an approximately equal percentage of pollen characteristic of two types of climate the inference is drawn that an intermediate type of climate existed during the deposition of the stratum; and where one finds a very low percentage of pollen characteristic of any type of climate, one concludes that that climate did not exist during the deposition of that stratum. The question has been raised as to the number of grains that need to be counted in order to obtain a sufficiently reliable count for climatic interpretation. Sears ('30) counts 100 to 200, Erdtman ('31) 150, Lewis and Cocke ('29) 800, and Bowman ('31) 1000 to 1800 from each depth. One practical test for the reliability of a set of data is to take two samples of the data, and obtain the coefficient of reliability 2(i.e. the Pearson correla-
Quantifying the relative performance of two undetected‐extinction models

Extinctions of undiscovered species (undetected extinctions) constitute a portion of biodiversity loss that is often ignored. We compared the performance of 2 models of undetected extinctions – Tedesco and SEUX – when estimating undetected extinctions with both simulated and real‐world data. We generated simulated data by considering a birth‐death process in which less abundant species were more likely to go extinct. When detection rates were higher for common species, the 2 models underestimated the true number of undetected extinctions by up to 88.7%, and when detection rates were independent of abundance, the 2 models performed better; the SEUX model had an average bias of +3.1% and the Tedesco model had an average bias of −62.3%. We applied the models to 8 real‐world data sets (e.g., Australian amphibians, Australian birds, North American bivalves) and found that true extinctions may be from 15% to 180% higher than observed values. For 6 of the 8 data sets, the SEUX model yielded absolute estimates that were 5.7–66.8% lower than those of the Tedesco model. We mainly attributed this difference to the SEUX model's assumption that there are no undetected extant species currently. We assessed the accuracy of the models’ estimates with a logistic regression to test whether detection and extinction rates were uncorrelated across species. Rates were correlated for 3 of the 8 data sets; species discovered later had a higher probability of being extinct, suggesting that extinction numbers could be even higher for these groups. Despite caveats associated with the models, the evidence from both show biodiversity loss in these groups may be more severe than what has been documented.
Iron Oxide Nanoparticles as Carriers for DOX and Magnetic Hyperthermia after Intratumoral Application into Breast Cancer in Mice: Impact and Future Perspectives

There is still a need for improving the treatment of breast cancer with doxorubicin (DOX). In this paper, we functionalized magnetic nanoparticles (MNPs) with DOX and studied the DOX-induced antitumor effects in breast cancer cells (BT474) in the presence of magnetic hyperthermia (43 °C, 1 h). We show that i) intratumoral application of DOX-functionalized MNPs (at least at a concentration of 9.6 nmol DOX/100 mm3 tumor volume) combined with magnetic hyperthermia favors tumor regression in vivo, and there is evidence for an increased effect compared to magnetic hyperthermia alone or to the intratumoral application of free DOX and ii) the presence of the pseudopeptide NucAnt (N6L) on the MNP surface might well be beneficial in its function as carrier for MNP internalization into breast cancer cells in vitro, which could further augment the possibility of the induction of intracellular heating spots and cell death in the future.
International Union of Basic and Clinical Pharmacology. CVIII. Calcium-Sensing Receptor Nomenclature, Pharmacology, and Function

The calcium-sensing receptor (CaSR) is a class C G protein–coupled receptor that responds to multiple endogenous agonists and allosteric modulators, including divalent and trivalent cations, L-amino acids, γ-glutamyl peptides, polyamines, polycationic peptides, and protons. The CaSR plays a critical role in extracellular calcium (Ca2+o) homeostasis, as demonstrated by the many naturally occurring mutations in the CaSR or its signaling partners that cause Ca2+o homeostasis disorders. However, CaSR tissue expression in mammals is broad and includes tissues unrelated to Ca2+o homeostasis, in which it, for example, regulates the secretion of digestive hormones, airway constriction, cardiovascular effects, cellular differentiation, and proliferation. Thus, although the CaSR is targeted clinically by the positive allosteric modulators (PAMs) cinacalcet, evocalcet, and etelcalcetide in hyperparathyroidism, it is also a putative therapeutic target in diabetes, asthma, cardiovascular disease, and cancer. The CaSR is somewhat unique in possessing multiple ligand binding sites, including at least five putative sites for the “orthosteric” agonist Ca2+o, an allosteric site for endogenous L-amino acids, two further allosteric sites for small molecules and the peptide PAM, etelcalcetide, and additional sites for other cations and anions. The CaSR is promiscuous in its G protein–coupling preferences, and signals via Gq/11, Gi/o, potentially G12/13, and even Gs in some cell types. Not surprisingly, the CaSR is subject to biased agonism, in which distinct ligands preferentially stimulate a subset of the CaSR’s possible signaling responses, to the exclusion of others. The CaSR thus serves as a model receptor to study natural bias and allostery. Significance Statement The calcium-sensing receptor (CaSR) is a complex G protein–coupled receptor that possesses multiple orthosteric and allosteric binding sites, is subject to biased signaling via several different G proteins, and has numerous (patho)physiological roles. Understanding the complexities of CaSR structure, function, and biology will aid future drug discovery efforts seeking to target this receptor for a diversity of diseases. This review summarizes what is known to date regarding key structural, pharmacological, and physiological features of the CaSR.
Capacitance Enhancement by Incorporation of Functionalised Carbon Nanotubes into Poly(3,4-Ethylenedioxythiophene)/Graphene Oxide Composites

This paper reports on the role of oxidised carbon nanotubes (oxMWCNTs) present in poly-3,4-ethylenedioxytiophene (PEDOT)/graphene oxide (GOx) composite. The final ternary composites (pEDOT/GOx/oxMWCNTs) are synthesised by an electrodeposition process from the suspension-containing monomer, oxidised carbon nanotubes and graphene oxide. Dissociated functional groups on the surface of graphene oxide play a role of counter-ions for the polymer chains. Detailed physicochemical and electrochemical characterisation of the ternary composites is presented in the paper. The results prove that the presence of oxMWCNTs in the ternary composites doubles the capacitance values compared to the binary ones (450 vs. 270 F cm−3 for PEDOT/GOx/oxMWCNTs and PEDOT/GOx, respectively). The amount of carbon nanotubes in the synthesis solution is crucial for physicochemical properties of the composites, their adhesion to the electrode substrate and the electrochemical performance.
Unifying developmental programs for embryonic and postembryonic neurogenesis in the zebrafish retina

ABSTRACT The zebrafish retina grows for a lifetime. Whether embryonic and postembryonic retinogenesis conform to the same developmental program is an outstanding question that remains under debate. Using single-cell RNA sequencing of ∼20,000 cells of the developing zebrafish retina at four different stages, we identified seven distinct developmental states. Each state explicitly expresses a gene set. Disruption of individual state-specific marker genes results in various defects ranging from small eyes to the loss of distinct retinal cell types. Using a similar approach, we further characterized the developmental states of postembryonic retinal stem cells (RSCs) and their progeny in the ciliary marginal zone. Expression pattern analysis of state-specific marker genes showed that the developmental states of postembryonic RSCs largely recapitulated those of their embryonic counterparts, except for some differences in rod photoreceptor genesis. Thus, our findings reveal the unifying developmental program used by the embryonic and postembryonic retinogenesis in zebrafish. Summary: Single-cell RNA-sequencing identifies a repertoire of genetically defined developmental states conserved by embryonic and postembryonic retinal neurogenesis.
The toxicology of cocoa and methylxanthines: A review of the literature

Abstract The critical review of the literature cited on pharmacology, toxicology, metabolism, and safety assessment clearly demonstrates that cocoa per se has not attracted a great deal of scientific interest because of its long-term usage with no reported adverse effects that would be injurious to man. On the other hand, a great deal of research has been directed towards understanding the pharmacological properties of the methylxanthines--caffeine, theobromine, and theophylline. Much of the emphasis on metabolism, toxicology, teratogenic potential, and safety assessment has been on the evaluation of caffeine. In light of the serious health concerns ascribed to the effects of caffeine and the lack of basic information on theobromine and theophylline, it is imperative that a major research program be undertaken to evaluate these methylxanthines and, of course, cocoa, coffee, and tea. It only will be through elucidating their mechanism of action that we will be in a position to assess their safety. Before committing research efforts to evaluating the long-term effects of these methylxanthines and their respective foodstuffs, which serve as our primary source of exposure, it is critical to initiate more basic research on the metabolism of caffeine, theophylline, and theobromine in several animal species and man. While published reports do appear in this area, it is essential to understand fully the similarities and differences between various animals and man. The influence of dietary factors and drug interactions must also be determined. Before establishing dosage levels for a chronic toxicity study, the pharmacokinetics of the dose must be determined in the species that will be used in long-term studies. This is necessary if there is a dose-dependency in the animal above which saturation may occur and the plasma half-life kinetics change, or shifts occur either in the metabolic pathways of degradation and/or in the route of excretion from the body. The area of teratology must also be thoroughly evaluated. Studies undertaken should include identification and quantitation of the metabolites of caffeine, theophylline, and theobromine in the pregnant animal, the respective pharmacokinetics of each compound, dose-dependency (if this is the case), and their potential teratogenicity. In addition, the influence of other drugs or dietary variables must be included. In addition to teratology, a great deal of research is needed to assess and quantitate fetal and neonatal metabolism of these compounds. (ABSTRACT TRUNCATED AT 400 WORDS)
Significance of PI3K signalling pathway in clear cell renal cell carcinoma in relation to VHL and HIF status

Renal cell carcinoma (RCC) includes diverse tumour types characterised by various genetic abnormalities. The genetic changes, like mutations, deletions and epigenetic alterations, play a crucial role in the modification of signalling networks, tumour pathogenesis and prognosis. The most prevalent RCC type, clear cell RCC (ccRCC), is asymptomatic in the early stages and has a poorer prognosis compared with the papillary and the chromophobe types RCCs. Generally, ccRCC is refractory to chemotherapy and radiation therapy. Loss of von Hippel-Lindau (VHL) gene and upregulation of hypoxia-inducible factors (HIF), the signature of most sporadic ccRCC, promote multiple growth factors. Hence, VHL/HIF and a variety of pathways, including phosphatase and TEnsin homolog on chromosome 10/phosphatidylinositol-3-kinase (PI3K)/AKT, are closely connected and contribute to the ontogeny of ccRCC. In the recent decade, multiple targeting agents have been developed based on blocking major signalling pathways directly or indirectly involved in ccRCC tumour progression, metastasis, angiogenesis and survival. However, most of these drugs have limitations; either metastatic ccRCC develops resistance to these agents, or despite blocking receptors, tumour cells use alternate signalling pathways. This review compiles the state of knowledge about the PI3K/AKT signalling pathway confined to ccRCC and its cross-talks with VHL/HIF pathway.
Beyond depression, anxiety and post-traumatic stress disorder symptoms: Qualitative study of negative emotional experiences in hematopoietic stem cell transplant patients.

OBJECTIVE Psychological distress impacts a variety of health outcomes in hematopoietic stem cell transplantation (HSCT). Focused qualitative studies on a wider range of psychological distress in HSCT patients are lacking. However, understanding the subtleties of psychological distress (e.g. fear, guilt, loss of control) in HSCT patients is imperative to optimising the psychological well-being of this vulnerable population. To explore psychological distress after transplantation, we conducted semi-structured interviews with 25 HSCT patients. METHODS Interviews were completed in the first 100 days after transplantation. Interview modules explored psychological distress symptoms in the hospital and during the first 100 days after HSCT, along with the perceived impact of these symptoms on their recovery. RESULTS Of the negative emotional experiences reported, feeling trapped, fear, guilt, discouragement and powerlessness were frequently expressed. Patients reported that negative emotional states interfered with their motivation to participate in health behaviours important to the transplant recovery. CONCLUSION As one of the few qualitative studies broadly characterising the nature of negative emotional experiences after HSCT, these findings add to our understanding of the specific psychological challenges in this growing patient population and can inform development of targeted interventions and overall management of psychological distress during HSCT recovery.
Solid lipid nanoparticles enhanced the neuroprotective role of curcumin against epilepsy through activation of Bcl-2 family and P38 MAPK pathway.

Oxidative stress of neurons caused by a series of complex neuropathological processes, will induce certain neurodegenerative disorders including epilepsy. Curcumin (Cur) is an effective natural anti-oxidant compound, however, the poor bioavailability obstructs its neural protective applications. In this study, Cur is encapsulated in solid lipid nanoparticles (SLNs) for better neuroprotective efficacy. In vitro study certified that Cur-SLNs functioned obviously better against neuronal apoptosis than Cur, by significantly decreasing the level of free radical and reversing mitochondrial function through the activation of Bcl-2 family. In vivo experiments showed that SLNs transported Cur through the blood-brain barrier(BBB). The behavioural performance of epileptic mice was improved by Cur-SLNs, with more NeuN but less TUNEL positive cells observed in hippocampus. In vivo mechanism was also explored. Cur-SLNs reduced neuronal apoptosis through Bcl2 family and P38 MAPK pathways. Overall, Cur-SLNs have better protective effects on oxidative stress neurons than free Cur both in vitro and in vivo, which suggests it a promising agent against neurodegenerative disorders including epilepsy.
Genetic biogeography of the rare “copper moss,” Mielichhoferia elongata (Bryaceae)

Mielichhoferia elongata, one of the so-called "copper mosses," has a broad but highly disjunctive geographic distribution and is rare throughout its range. A genetic analysis of 30 populations based on a survey of 21 allozyme loci reveals the following. 1) Total gene diversity at the specific level is high (0.41). -2) Within-population diversity is low, and over 90% of all genetic variation is among rather than within populations (mean GST = 0.93). 3) There is little differentiation in allele frequencies between North American and European populations. 4) Populations consist of one to six multilocus genotypes; 13 of the populations appear to consist of a single clone. 5) Colorado populations contain a tremendous reservoir of genetic variation (88% of all alleles found in the species in North America and Europe occur in one or more Colorado populations). 6) Populations in the eastern and western United States, and in Europe, contain subsets of the allelic diversity found in Colorado. The genetic structure of M. elongata suggests repeated dispersal and founding of populations.
Stalking the Wild Mustard

Arabidopsis thaliana is not just for plant biologists anymore. A few intrepid ecologists and evolutionary biologists are now touting its merits as a system in which to study the genetic basis of the traits they study. The newly completed genome sequence is allowing researchers to connect the genotype--an organism9s particular mix of genes--with its phenotype--how that organism develops and acts--in ways that have not been possible in other organisms whose genetics are not as well known.
The Effects of Cadmium Toxicity

Cadmium (Cd) is a toxic non-essential transition metal that poses a health risk for both humans and animals. It is naturally occurring in the environment as a pollutant that is derived from agricultural and industrial sources. Exposure to cadmium primarily occurs through the ingestion of contaminated food and water and, to a significant extent, through inhalation and cigarette smoking. Cadmium accumulates in plants and animals with a long half-life of about 25–30 years. Epidemiological data suggest that occupational and environmental cadmium exposure may be related to various types of cancer, including breast, lung, prostate, nasopharynx, pancreas, and kidney cancers. It has been also demonstrated that environmental cadmium may be a risk factor for osteoporosis. The liver and kidneys are extremely sensitive to cadmium’s toxic effects. This may be due to the ability of these tissues to synthesize metallothioneins (MT), which are Cd-inducible proteins that protect the cell by tightly binding the toxic cadmium ions. The oxidative stress induced by this xenobiotic may be one of the mechanisms responsible for several liver and kidney diseases. Mitochondria damage is highly plausible given that these organelles play a crucial role in the formation of ROS (reactive oxygen species) and are known to be among the key intracellular targets for cadmium. When mitochondria become dysfunctional after exposure to Cd, they produce less energy (ATP) and more ROS. Recent studies show that cadmium induces various epigenetic changes in mammalian cells, both in vivo and in vitro, causing pathogenic risks and the development of various types of cancers. The epigenetics present themselves as chemical modifications of DNA and histones that alter the chromatin without changing the sequence of the DNA nucleotide. DNA methyltransferase, histone acetyltransferase, histone deacetylase and histone methyltransferase, and micro RNA are involved in the epigenetic changes. Recently, investigations of the capability of sunflower (Helianthus annuus L.), Indian mustard (Brassica juncea), and river red gum (Eucalyptus camaldulensis) to remove cadmium from polluted soil and water have been carried out. Moreover, nanoparticles of TiO2 and Al2O3 have been used to efficiently remove cadmium from wastewater and soil. Finally, microbial fermentation has been studied as a promising method for removing cadmium from food. This review provides an update on the effects of Cd exposure on human health, focusing on the cellular and molecular alterations involved.