Miracle-dz/UniFAR-FTUs huggingface dataset:
Does climate limit species richness by limiting individual species’ ranges?

Broad-scale geographical variation in species richness is strongly correlated with climate, yet the mechanisms underlying this correlation are still unclear. We test two broad classes of hypotheses to explain this pattern. Bottom-up hypotheses propose that the environment determines individual species’ ranges. Ranges then sum up to yield species richness patterns. Top-down hypotheses propose that the environment limits the number of species that occur in a region, but not which ones. We test these two classes of hypotheses using a natural experiment: seasonal changes in environmental variables and seasonal range shifts of 625 migratory birds in the Americas. We show that richness seasonally tracks the environment. By contrast, individual species’ geographical distributions do not. Rather, species occupy different sets of environmental conditions in two seasons. Our results are inconsistent with extant bottom-up hypotheses. Instead, a top-down mechanism appears to constrain the number of species that can occur in a given region.
Evidence for sodium‐calcium exchange in the guinea‐pig ureter.

The effects of high‐K and low‐Na solutions on the smooth muscle of the guinea‐pig ureter have been examined in both normal tissues, and tissues in which the Na pump had been blocked by exposure to K‐free solutions or ouabain (high‐Na tissues). Tension recording, membrane potential measurements and ion analysis were used. High‐K solutions depolarize normal tissues, leading to action potential generation and phasic contractions followed, at concentrations greater than 20‐30 mM, by cessation of action potentials and the development of a biphasic contracture which declines slowly during continuous exposure. The contracture is abolished by Ca‐antagonist drugs, procaine and Ca‐free solutions. Short exposures of normal tissues to Na‐free solutions do not result in tension development. Longer exposures may initiate tension, depending on the Na substitute used. Sucrose causes depolarization of the cells and spike development associated with phasic contractions, superimposed on a small contracture; Li depolarizes the cells but causes no tension generation; Tris hyperpolarizes the cells and a small increase in basal tone may be seen. On exposure to K‐free solutions or ouabain, the tissues do not develop significant tone but their response to short application of high‐K solutions grows with time. The tissues also develop the ability to contract on short applications of low‐Na solutions. The low‐Na contractures are resistant to concentrations of Ca antagonists that abolish the K responses of normal tissues, but are abolished in Ca‐free solutions. The ability of the tissues to contract in Na‐free solutions is accompanied by an increase in intracellular Na and loss of intracellular K. Even after several hours' exposure to ouabain, however, the tissues still contain significant amounts of K and the membrane potential is the same as, or more negative than that in normal tissues. Therefore it appears that another mechanism, apart from the Na pump, can regulate intracellular Na. On continuous exposure to Na‐free solutions, the contracture declines rapidly. The decline is associated with a loss of intracellular Na. The Na‐free contracture is larger when K rather than Tris is used as the substitute. This difference persists in the presence of a concentration of Mn that abolishes the K contracture of normal tissues but is abolished by high concentrations (10 mM) of procaine. (ABSTRACT TRUNCATED AT 400 WORDS)
Comparative Performance of Linear Multielectrode Probes and Single-Tip Electrodes for Intracortical Microstimulation and Single-Neuron Recording in Macaque Monkey

Intracortical microstimulation (ICMS) is one of the most widely employed techniques for providing causal evidence of the relationship between neuronal activity and specific motor, perceptual, or even cognitive functions. In recent years, several new types of linear multielectrode silicon probes have been developed, allowing researchers to sample neuronal activity at different depths along the same cortical site simultaneously and with high spatial precision. Nevertheless, silicon multielectrode probes have been rarely employed for ICMS studies and, more importantly, it is unknown whether and to what extent they can be used for combined recording and stimulation experiments. Here, we addressed these issues during both acute and chronic conditions. First, we compared the behavioral outcomes of ICMS delivered to the hand region of a monkey's motor cortex with multielectrode silicon probes, commercially available multisite stainless-steel probes and single-tip glass-coated tungsten microelectrodes. The results for all three of the probes were reliable and similar. Furthermore, we tested the impact of long-train ICMS delivered through chronically implanted silicon probes at different time intervals, from 1 to 198 days after ICMS sessions, showing that although the number of recorded neurons decreased over time, in line with previous studies, ICMS did not alter silicon probes' recording capabilities. These findings indicate that in ICMS experiments, the performance of linear multielectrode silicon probes is comparable to that of both single-tip and multielectrode stainless-steel probes, suggesting that the silicon probes can be successfully used for combined recording and stimulation studies in chronic conditions.
Increased Activation of L‐Type Voltage‐Dependent Calcium Channels Is Associated with Glycine Enhancement of N‐Methyl‐d‐Aspartate‐Stimulated Dopamine Release in Global Cerebral Ischemia/Reperfusion

Abstract: We investigated the relationships among N‐methyl‐d‐aspartate, glycine, L‐type voltage‐dependent calcium channels, and [3H]dopamine release in a canine model of global cerebral ischemia/reperfusion. The binding of [3H]PN200‐110 ([3H]isradipine) to L‐type voltage‐dependent calcium channels, that open as a consequence of N‐methyl‐d‐aspartate‐induced changes in membrane potential, was approximately doubled in striatal membranes prepared from ischemic animals relative to controls, and remained significantly elevated at 30 min and 2 h of reperfusion. These changes coincided temporally with changes in the ability of the voltage‐sensitive calcium channel blocker nitrendipine to inhibit glycine enhancement of N‐methyl‐d‐aspartate‐stimulated [3H]dopamine release in striatal slices prepared from the same animals. Compared with nonischemic controls, N‐methyl‐d‐aspartate‐stimulated [3H]dopamine release was increased in ischemic animals and remained increased throughout reperfusion up to at least 24 h. Glycine enhanced N‐methyl‐d‐aspartate‐stimulated release in all treatment groups. The enhancement of N‐methyl‐d‐aspartate‐stimulated dopamine release by glycine was reduced by the inclusion of nitrendipine in striatal slices from ischemic and 30‐min reperfused animals. These data suggest that glycine may facilitate opening of the voltage‐dependent calcium channels activated by N‐methyl‐d‐aspartate and that this facilitation is blocked by the antagonist nitrendipine.
Pili mediate specific adhesion of Streptococcus pyogenes to human tonsil and skin

Very little is known about the biological functions of pili that have recently been found to be expressed by important Gram‐positive pathogens such as Corynebacterium diphtheriae, Streptococcus agalacticae, S. pneumoniae and S. pyogenes. Using various ex vivo tissue and cellular models, here we show that pili mediate adhesion of serotype M1 S. pyogenes strain SF370 to both human tonsil epithelium and primary human keratinocytes, which represent the two main sites of infection by this human‐specific pathogen. Mutants lacking minor pilus subunits retained the ability to express cell‐surface pili, but these were functionally defective. In contrast to above, pili were not required for S. pyogenes adhesion to either immortalized HEp‐2 or A549 cells, highlighting an important limitation of these extensively used adhesion/invasion models. Adhering bacteria were internalized very effectively by both HEp‐2 and A549 cells, but not by tonsil epithelium or primary keratinocytes. While pili acted as the primary adhesin, the surface M1 protein clearly enhanced adhesion to tonsil, but surprisingly, had the opposite effect on adhesion to keratinocytes. These studies provide clear evidence that S. pyogenes pili display an adhesive specificity for clinically relevant human tissues and are likely to play a critical role in the initial stages of infection.
Bh3 induced conformational changes in Bcl‐Xl revealed by crystal structure and comparative analysis

Apoptosis or programmed cell death is a regulatory process in cells in response to stimuli perturbing physiological conditions. The Bcl‐2 family of proteins plays an important role in regulating homeostasis during apoptosis. In the process, the molecular interactions among the three members of this family, the pro‐apoptotic, anti‐apoptotic and BH3‐only proteins at the mitochondrial outer membrane define the fate of a cell. Here, we report the crystal structures of the human anti‐apoptotic protein Bcl‐XL in complex with BH3‐only BIDBH3 and BIMBH3 peptides determined at 2.0 Å and 1.5 Å resolution, respectively. The BH3 peptides bind to the canonical hydrophobic pocket in Bcl‐XL and adopt an alpha helical conformation in the bound form. Despite a similar structural fold, a comparison with other BH3 complexes revealed structural differences due to their sequence variations. In the Bcl‐XL‐BIDBH3 complex we observed a large pocket, in comparison with other BH3 complexes, lined by residues from helices α1, α2, α3, and α5 located adjacent to the canonical hydrophobic pocket. These results suggest that there are differences in the mode of interactions by the BH3 peptides that may translate into functional differences in apoptotic regulation. Proteins 2015; 83:1262–1272. © 2015 Wiley Periodicals, Inc.
Distribution of Orexin/Hypocretin Immunoreactivity in the Brain of the Lungfishes Protopterus dolloi and Neoceratodus forsteri

Lungfishes are currently considered the closest living relatives of tetrapods and represent an interesting group for the study of evolutionary traits in the transition from fishes to tetrapods. The brains of lungfishes have received little attention in comparative studies probably due to the difficulty of obtaining these unique animals. In the present study the distribution of orexin (hypocretin)-like immunoreactivity was studied in the brain of the African lungfish Protopterus dolloi and the Australian lungfish Neoceratodus forsteri by using antibodies directed against the mammalian orexin-A and orexin-B peptides. Simultaneous detection of orexins and tyrosine hydroxylase or serotonin was used to assess the precise location of the orexins in the brain and to evaluate the possible influence of the orexin system on the monoaminergic cell groups. Although some differences were noted, a common pattern for the distribution of orexins in the two lungfishes studied was observed. In both species, most immunoreactive neurons were observed in the suprachiasmatic nucleus and dorsal hypothalamus. Only in Neoceratodus, however, were important cell populations found in the preoptic area and infundibular hypothalamus, whereas small numbers of faintly reactive neurons were present in the lateral septum and ventral striatum. Fiber labeling was widely distributed in all main brain subdivisions, but was more abundant in regions such as the septum, preoptic area, suprachiasmatic nucleus, lateral hypothalamic area, thalamus, pretectum and tegmentum. Less conspicuous was the innervation of the pallial regions, habenula, optic tectum, rhombencephalic reticular formation and spinal cord. Orexinergic innervation was found in close contact with dopaminergic, noradrenergic and serotoninergic cell groups, homologous to the substantia nigra in the midbrain tegmentum, the locus coeruleus, the nucleus of the solitary tract and the raphe nuclei. Although unique features have been found for lungfishes, the location of orexin immunoreactive elements is largely consistent with that recently reported following a similar approach in amphibians and amniotes, suggesting that the general organization of this peptidergic system occurred in the common ancestor of lungfishes and tetrapods.
Patterns and harms of pharmaceutical drug use among ecstasy users in Australia.

BACKGROUND There has been a significant incursion of prescription drugs in to the club scene worldwide. The concomitant use of ecstasy and pharmaceutical drugs is associated with potentially serious health-related harms. This has ramifications for people who deliberately combine pharmaceutical drugs with ecstasy to achieve a specific effect and for people legitimately using pharmaceutical drugs for a health condition who may incidentally use ecstasy. This exploratory study had the broad aim to investigate the patterns and harms of concomitant use of pharmaceutical drugs and ecstasy, and to explore participants' experiences when visiting a General Practitioner (GP). METHODS In-depth interviews were conducted with 30 ecstasy/pharmaceutical drug users. RESULTS Users reported deliberately combining stimulants (dexamphetamine, methylphenidate (e.g. Ritalin), antidepressants and sildenafil (e.g. Viagra) for non-medical purposes with ecstasy. A wide range of effects were reported. Several clear relationships emerged between the use of pharmaceutical drugs and ecstasy, and the distinctions between these in terms of motivations for use and consequences are discussed. The attitudes of GPs were professional and non-judgemental and there was little reluctance among participants to disclose illicit drug use. Screening for illicit drug use was limited. IMPLICATIONS Findings have important implications for clubbers in regard to harm reduction strategies and highlight a number of areas for future research.
Replication and Recombination of Gene 59 Mutant of Bacteriophage T4D

After infection of Escherichia coli B with phage T4D carrying an amber mutation in gene 59, recombination between two rII markers is reduced two- to three-fold. This level of recombination deficiency persists even when burst size similar to wild type is induced by the suppression of the mutant DNA-arrest phenotype. In the background of two other DNA-arrest mutants in genes 46 and 47, a 10- to 11-fold reduction in recombination is observed. The cumulative effect of gene 59 mutation on gene 46-47 mutant suggests that complicated interactions must occur in the production of genetic recombinants. The DNA-arrest phenotype of gene 59 mutant can be suppressed by inhibiting the synthesis of late phage proteins. Under these conditions, DNA replicative intermediates similar to those associated with wild-type infection are induced. Synthesis of late phage proteins, however, results in the degradation of mutant 200S replicative intermediate into 63S DNA molecules even in the absence of capsid assembly. Although these 63S molecules are associated with membrane, they do not replicate. These results suggest a role for gene 59 product, in addition to a possible requirement of concatemeric DNA in late replication of phage T4 DNA.
Interleukin 6 expression by Hodgkin/Reed–Sternberg cells is associated with the presence of ‘B’ symptoms and failure to achieve complete remission in patients with advanced Hodgkin's disease

Summary. Interleukin 6 (IL‐6) is a potent immunomodulatory cytokine that has pathogenic and prognostic significance in a number of disorders. Previous studies in Hodgkin's disease (HD) have demonstrated the association between elevated serum levels of IL‐6 and unfavourable prognosis, including advanced stage and the presence of ‘B’ symptoms and with reduced survival. Although IL‐6 expression has been demonstrated in both the malignant Hodgkin/Reed–Sternberg (HRS) cells and in the various non‐malignant cells present in HD biopsies, a relationship between expression of IL‐6 by the tumour and outcome measures has not been established. The study group comprised of 97 patients with advanced HD who were recruited to two related clinical trials. IL‐6 expression was determined on paraffin‐wax sections of biopsy material by means of an immunohistochemical assay. Of the 97 patients, 27 (28%) showed staining for IL‐6 in HRS cells. IL‐6 expression by HRS cells was significantly correlated with a decreased likelihood of achieving a complete response to chemotherapy (P = 0·02) and with an increased prevalence of ‘B’ symptoms (P = 0·04). IL‐6 expression by HRS cells was not associated with Epstein–Barr virus status (P = 0·57). In summary, the results suggest that IL‐6 expression by HRS cells may contribute to the presence of ‘B’ symptoms and to a decreased likelihood to achieve a complete remission in HD patients.
Equilibrium Rate Analysis in Supply Chain Financial Management

This paper addresses Supply Chain Financial Management (SCFM), namely, the analysis of combined operational and financial aspects of supply chains, an important emerging topic in Supply Chain Management (SCM). It further aims to bridge the gap between practical SCM research and analytical tools for modeling and optimization purposes by illustrating how analytical and numerical methods can be used in combination with simple financial and accounting concepts to obtain financial/accounting metrics for supply chains. To this end we introduce Equilibrium Rate Analysis (ERA) as a modeling approach to stochastic systems and their performance metrics, including the domain of SCFM. ERA posits stochastic equilibrium as the mathematical setting of models, and utilizes rate metrics instead of cumulative (time-additive) ones. This approach brings about major conceptual and computational simplifications, which facilitate evaluation and optimization of SCFM metrics. The paper explains in broad outline how to formulate ERA-based models and illustrates derivation of SCFM metrics, focusing on analytical and numerical methodologies in Markovian models.
Surgical skills training: simulation and multimedia combined

Basic surgical skills are needed throughout the medical profession, but current training is haphazard and unpredictable. There is increasing pressure to provide transparency about training and performance standards. There is a clear need for inexperienced learners to build a framework of basic skills before carrying out surgical procedures on patients. Effective learning of a skill requires sustained deliberate practice within a cognitive framework, and simulation offers an opportunity for safe preparation.
Development of the Proteasome Inhibitor Velcade™ (Bortezomib)

The dipeptide boronic acid analogue VELCADE™ (Bortezomib; formerly known as PS-341, LDP-341 and MLM341) is a potent and selective inhibitor of the proteasome, a multicatalytic enzyme that mediates many cellular regulatory signals by degrading regulatory proteins or their inhibitors. The proteasome is, thus, a potential target for pharmacological agents. Bortezomib, the first proteasome inhibitor to reach clinical trials, has shown in vitro and in vivo activity against a variety of malignancies, including myeloma, chronic lymphocytic leukemia, prostate cancer, pancreatic cancer, and colon cancer. The drug is rapidly cleared from the vascular compartment, but a novel pharmacodynamic assay has shown that bortezomib–mediated proteasome blockade is dose-dependent and reversible. Based on phase I studies demonstrating that bortezomib has manageable toxicities in patients with advanced cancers, phase II trials have been initiated for both solid and hematological malignancies.
Inhibitory effect of phenethyl isothiocyanate against benzo[a] pyrene-induced rise in CYP1A1 mRNA and apoprotein levels as its chemopreventive properties.

BACKGROUND Phenethyl isothiocyanate (PEITC), the most comprehensively studied aromatic isothiocyanate, has been shown to act as an anti-cancer agent mainly through modulation of biotransformation enzymes responsible for metabolizing carcinogens in the human body. Humans are often exposed to carcinogenic factors, some of which through the diet, such as polycyclic aromatic hydrocarbon benzo[a]pyrene via the consumption of over-cooked meats. Inhibition of the enzymes responsible for the bioactivation of this carcinogen, for example CYP1A1, the major enzyme required for polycyclic aromatic hydrocarbons (PAHs) bioactivation, is recognized as a chemoprevention strategy. OBJECTIVE To evaluate the inhibitory effects of PEITC against benzo[a]pyrene-induced rise in rat liver CYP1A1 mRNA and apoprotein levels. MATERIALS AND METHODS Precision cut rat liver slices were treated with benzo[a]pyrene at 1 and 5 μM in the presence of PEITC (1-25 μM) for 24 hours, followed by determination of CYP1A1 mRNA and apoprotein levels using quantitative polymerase chain reaction and immunoblotting. RESULTS Findings revealed that PEITC inhibited benzo[a]pyrene-induced rise in rat liver CYP1A1 mRNA in a dose-dependent manner as well as the apoprotein levels of CYP1A. CONCLUSIONS It was demonstrated that PEITC can directly inhibit the bioactivation of benzo[a]pyrene, indicating chemopreventive potential.
Multistage Stochastic Optimization for Production‐Inventory Planning with Intermittent Renewable Energy

A growing number of companies install wind and solar generators in their energy‐intensive facilities to attain low‐carbon manufacturing operations. However, there is a lack of methodological studies on operating large manufacturing facilities with intermittent power. This study presents a multi‐period, production‐inventory planning model in a multi‐plant manufacturing system powered with onsite and grid renewable energy. Our goal is to determine the production quantity, the stock level, and the renewable energy supply in each period such that the aggregate production cost (including energy) is minimized. We tackle this complex decision problem in three steps. First, we present a deterministic planning model to attain the desired green energy penetration level. Next, the deterministic model is extended to a multistage stochastic optimization model taking into account the uncertainties of renewables. Finally, we develop an efficient modified Benders decomposition algorithm to search for the optimal production schedule using a scenario tree. Numerical experiments are carried out to verify and validate the model integrity, and the potential of realizing high‐level renewables penetration in large manufacturing system is discussed and justified.
Antioxidant and antiglycation properties of total saponins extracted from traditional Chinese medicine used to treat diabetes mellitus

Eleven antidiabetic traditional Chinese medicine (TCM) extracts rich in saponins were examined for their antioxidant and antiglycation activities. The antioxidant activities of these extracts were evaluated by studying the inhibition of lipid peroxidation in rat liver microsomes induced by ascorbate/Fe2+, cumine hydroperoxide (CHP) or CCl4/reduced form of nicotinamide‐adenine dinucleotide phosphate (NADPH). The antioxidant capacities were also evaluated by studying the scavenging of 2,2′‐diphenyl‐1‐picrylhydrazyl (DPPH) free radical. The antiglycation activities of these extracts were evaluated by hemoglobin‐δ‐gluconolactone (δ‐Glu) assay, bovine serum albumin (BSA)‐glucose assay and N‐acetyl‐glycyl‐lysine methyl ester (GK peptide)‐ribose assay. Aralia taibaiensis outperformed other extracts in most of the assays except inhibition of early glycation products formation, where Acanthopanax senticosus showed higher activity. Aralia taibaiensis was particularly potent in inhibiting the late glycation and formation of advanced glycation end products (AGEs) on proteins. The antioxidant and antiglycation activities of most extracts were correlated with the saponin content. The results demonstrate that the antidiabetic activities of most extracts could be explained, at least in part, by their combined antioxidant and antiglycation properties. Copyright © 2007 John Wiley & Sons, Ltd.