Miracle-dz/UniFAR-FTUs huggingface dataset:
Light-enhanced bioaccumulation of molybdenum by nitrogen-deprived recombinant anoxygenic photosynthetic bacterium Rhodopseudomonas palustris

As molybdenum (Mo) is an indispensable metal for plant nitrogen metabolisms, accumulation of dissolved Mo into bacterial cells may connect to the development of bacterial fertilizers that promote plant growth. In order to enhance Mo bioaccumulation, nitrogen removal and light illumination were examined in anoxygenic photosynthetic bacteria (APB) because APB possess Mo nitrogenase whose synthesis is strictly regulated by ammonium ion concentration. In addition, an APB, Rhodopseudomonas palustris, transformed with a gene encoding Mo-responsive transcriptional regulator ModE was constructed. Mo content was most markedly enhanced by the removal of ammonium ion from medium and light illumination while their effects on other metal contents were limited. Increases in contents of trace metals including Mo by the genetic modification were observed. Thus, these results demonstrated an effective way to enrich Mo in the bacterial cells by the culture conditions and genetic modification. Graphical abstract Mo content was specifically enhanced in N-deprived photosynthetic bacterium harboring a gene coding Mo-binding protein (FL, full-length; CT, Mo-binding domain; EV, vector).
Self-monitoring, systems, and chronic disease

We've all had patients who pay too much attention to their chronic conditions and breathlessly report every minor symptom or fluctuation. Others appear disconnected from their diseases and are genuinely surprised when informed that things aren't going well. In general, it seems desirable for patients to be actively involved in monitoring their health. But it turns out that if you have a chronic disease, sometimes it's a good idea to monitor yourself, and sometimes it may not be. George Stergiou and …
Experimental Studies on Reimplantation of Autogenous Bone Decalcified by Combined HCl and Ultrasonic Exposure

Decalcified bone implants induce new bone formation. In this experiment, the autogenous bone implant of canine mandible was treated by HCl under ultrasonic exposure for rapid decalcification. The aim of this study was to investigate the osteoinduction property of this rapidly decalcified bone reimplanted to the original site. The decalcified bone implant exhibited a similar degree of new formation to that of the fresh bone graft which was not subjected to decalcification. The results demonstrate that the combinational use of HCl and ultrasonic exposure for rapid decalcification treatment preserves the regenerative capacity of bone to be implanted.
In vitro selection of DNA aptamers binding pesticide fluoroacetamide

Fluoroacetamide (Mw = 77.06) is a lethal rodenticide to humans and animals which is still frequently abused in food storage somewhere in China. The production of antibodies for fluoroacetamide is difficult due to its high toxicity to animals, which limits the application of immunoassay method in poison detection. In this work, aptamers targeting N-fluoroacetyl glycine as an analog of fluoroacetamide were selected by a specific systematic evolution of ligands by exponential enrichment (SELEX) strategy. The binding ability of the selected aptamers to fluoroacetamide was identified using surface plasmon resonance (SPR)-based assay. The estimated KD values in the low micromolar range showed a good affinity of these aptamers to the target. Our work verified that the SELEX strategy has the potential for developing aptamers targeted to small molecular toxicants and aptamers can be employed as new recognition elements instead of antibodies for poison detection.
Macro advances in microRNAs and myocardial regeneration

Purpose of review Myocardial injury and disease often result in heart failure, a major cause of death worldwide. To achieve myocardial regeneration and foster development of efficient therapeutics for cardiac injury, it is essential to uncover molecular mechanisms that will promote myocardial regeneration. In this review, we examine the latest progress made in elucidation of the roles of small non-coding RNAs called microRNAs (miRs) in myocardial regeneration. Recent findings Promising progress has been made in studying cardiac regeneration. Several miRs, which include miR-590, miR-199a, miR-17-92 cluster, miR-199a-214 cluster, miR-34a, and miR-15 family, have been recently shown to play an essential role in myocardial regeneration by regulating different processes during cardiac repair, including cell death, proliferation, and metabolism. For example, miR-590 promotes cardiac regeneration through activating cardiomyocyte proliferation, whereas miR-34a inhibits cardiac repair through inducing apoptosis. Summary These recent findings shed new light on our understanding of myocardial regeneration and suggest potential novel therapeutic targets to treat cardiac disease.
Incidence, definition, diagnosis, and management of the cardiac resynchronization therapy nonresponder

Purpose of review Cardiac resynchronization therapy (CRT) reduces morbidity and mortality in patients with mild-to-severe heart failure. However, up to 40% of CRT recipients are nonresponders. This review addresses important aspects with regard to the identification and management of CRT nonresponders. Recent findings Mid-term clinical or echocardiographic nonresponse is associated with worse clinical outcomes during the extended follow-up. A number of predictors are indicative of CRT response, which include patient characteristics, electrical determinants, and imaging techniques from preimplant to postimplant period, and can be grouped as modifiable and nonmodifiable contributors to treatment response. Advanced age, male sex, ischemic cause, end-stage heart failure, inadequate electrical delay, and absence of mechanical dyssynchrony are regarded as unfavorable but nonmodifiable factors, for which considering underutilization of CRT by refining patient selection is reasonable. On the contrary, more efforts should be made to optimize patient management by correcting those modifiable factors, such as suboptimal medical therapy, uncontrolled atrial fibrillation, left ventricular lead dislodgement or inappropriate location, loss of biventricular capture, and lack of device optimization. Summary Proper management and careful selection of CRT recipients will transform a proportion of treatment nonresponders into responders, which is vital to improve patients’ outcome.
Aplysia synapse associated protein (APSAP): identification, characterization, and selective interactions with Shaker‐type potassium channels

The vertebrate post‐synaptic density (PSD) is a region of high molecular complexity in which dynamic protein interactions modulate receptor localization and synaptic function. Members of the membrane‐associated guanylate kinase (MAGUK) family of proteins represent a major structural and functional component of the vertebrate PSD. In order to investigate the expression and significance of orthologous PSD components associated with the Aplysia sensory neuron‐motor neuron synapse, we have cloned an Aplysia Dlg‐MAGUK protein, which we identify as Aplysia synapse associated protein (ApSAP). As revealed by western blot, RT‐PCR, and immunocytochemical analyses, ApSAP is predominantly expressed in the CNS and is located in both sensory neuron and motor neurons. The overall amino acid sequence of ApSAP is 55–61% identical to Drosophila Dlg and mammalian Dlg‐MAGUK proteins, but is more highly conserved within L27, PDZ, SH3, and guanylate kinase domains. Because these conserved domains mediate salient interactions with receptors and other PSD components of the vertebrate synapse, we performed a series of GST pull‐down assays using recombinant C‐terminal tail proteins from various Aplysia receptors and channels containing C‐terminal PDZ binding sequences. We have found that ApSAP selectively binds to an Aplysia Shaker‐type channel AKv1.1, but not to (i) NMDA receptor subunit AcNR1‐1, (ii) potassium channel AKv5.1, (iii) receptor tyrosine kinase ApTrkl, (iv) glutamate receptor ApGluR1/4, (v) glutamate receptor ApGluR2/3, or (vi) glutamate receptor ApGluR7. These findings provide preliminary information regarding the expression and interactions of Dlg‐MAGUK proteins of the Aplysia CNS, and will inform questions aimed at a functional analysis of how interactions in a protein network such as the PSD may regulate synaptic strength.
Evidence of Nurse Working Conditions: A Global Perspective

There is a global nursing shortage. Few health services decision makers have made the critical link between the number of human resources, the characteristics of the work environment and the impact on patients, nurses, and the system as a whole. The purpose of this article is to review evidence about nurse workload, staffing, skill mix, turnover, and organizational characteristics' effect on outcomes; discuss methodological considerations in this research; discuss research initiatives currently under way; review policy initiatives in different countries; and make recommendations where more research is needed. Overall, an understanding of the relationships among nurse staffing and organizational climate to patient safety and health outcomes is beginning to emerge in the literature. Little is known about nursing turnover and more evidence is needed with consistent definitions and control of underlying patient characteristics. Research and policy initiatives in Australia, Canada, New Zealand, and the United States are summarized.
Assessing hemodynamics noninvasively in patients with heart failure

Purpose of review Describe the contemporary assessment of cardiac hemodynamics using a comprehensive echo-Doppler examination in the heart failure (HF) patient. Recent findings Cardiac flow and filling pressures, on both the left and right sides of the heart, are fundamental to the accurate assessment of the HF patient. Accurate assessment of left ventricular (LV) and right ventricular (RV) systolic and diastolic function is necessary to establish, or exclude, HF as a cause or component of dyspnea in a given patient and to help determine causes of hemodynamic instability in HF patients. Variables such as spectral Doppler (mitral and tricuspid inflow, pulmonary and hepatic venous flow, and pulmonary valve regurgitation signal), tissue Doppler imaging, and speckle tracking, applied to the left and right heart, can help to accurately estimate cardiac hemodynamics. Summary A comprehensive echocardiogram with Doppler can provide an accurate assessment of left and right heart hemodynamics that is fundamental to the assessment and management of the HF patient.
Expression of 3‐hydroxyisobutyrate dehydrogenase in cultured neural cells

The branched‐chain amino acids (BCAAs) – isoleucine, leucine, and valine – belong to the limited group of substances transported through the blood–brain barrier. One of the functions they are thought to have in brain is to serve as substrates for meeting parenchymal energy demands. Previous studies have shown the ubiquitous expression of a branched‐chain alpha‐keto acid dehydrogenase among neural cells. This enzyme catalyzes the initial and rate‐limiting step in the irreversible degradative pathway for the carbon skeleton of valine and the other two branched‐chain amino acids. Unlike the acyl‐CoA derivates in the irreversible part of valine catabolism, 3‐hydroxyisobutyrate could be expected to be released from cells by transport across the mitochondrial and plasma membranes. This could indeed be demonstrated for cultured astroglial cells. Therefore, to assess the ability of neural cells to make use of this valine‐derived carbon skeleton as a metabolic substrate for the generation of energy, we investigated the expression in cultured neural cells of the enzyme processing this hydroxy acid, 3‐hydroxyisobutyrate dehydrogenase (HIBDH). To achieve this, HIBDH was purified from bovine liver to serve as antigen for the production of an antiserum. Affinity‐purified antibodies against HIBDH specifically recognized the enzyme in liver and brain homogenates. Immunocytochemistry demonstrated the ubiquitous expression of HIBDH among cultured glial (astroglial, oligodendroglial, microglial, and ependymal cells) and neuronal cells. Using an RT‐PCR technique, these findings were corroborated by the detection of HIBDH mRNA in these cells. Furthermore, immunofluorescence double‐labeling of astroglial cells with antisera against HIBDH and the mitochondrial marker pyruvate dehydrogenase localized HIBDH to mitochondria. The expression of HIBDH in neural cells demonstrates their potential to utilize valine imported into the brain for the generation of energy.
Expression of multiple AQP4 pools in the plasma membrane and their association with the dystrophin complex

Altered aquaporin‐4 (AQP4) expression has been reported in brain edema, tumors, muscular dystrophy, and neuromyelitis optica. However, the plasma membrane organization of AQP4 and its interaction with proteins such as the dystrophin‐associated protein complex are not well understood. In this study, we used sucrose density gradient ultracentrifugation and 2D blue native/sodium dodecyl sulfate–polyacrylamide gel electrophoresis and showed the expression of several AQP4 multi‐subunit complexes (pools) of different sizes, ranging from ≫ 1 MDa to ∼500 kDa and containing different ratios of the 30/32 kDa AQP4 isoforms, indicative of orthogonal arrays of particles of various sizes. A high molecular weight pool co‐purified with dystrophin and β‐dystroglycan and was drastically reduced in the skeletal muscle of mdx3cv mice, which have no dystrophin. The number and size of the AQP4 pools were the same in the kidney where dystrophin is not expressed, suggesting the presence of dystrophin‐like proteins for their expression. We found that AQP2 is expressed only in one major pool of ∼500 kDa, indicating that the presence of different pools is a peculiarity of AQP4 rather than a widespread feature in the AQP family. Finally, in skeletal muscle caveolin‐3 did not co‐purify with any AQP4 pool, indicating the absence of interaction of the two proteins and confirming that caveolae and orthogonal arrays of particles are two independent plasma membrane microdomains. These results contribute to a better understanding of AQP4 membrane organization and raise the possibility that abnormal expression of specific AQP4 pools may be found in pathological states.
Difructose anhydride III decreases body fat as a low-energy substitute or by decreasing energy intake in non-ovariectomized and ovariectomized female rats

We evaluated the effects of difructose anhydride III (DFAIII) on body weights of ovariectomized rats, which are a good model for obesity by estrogen deficiency-induced overeating. Female rats (10 weeks old) were subjected to ovariectomy or sham operation and then fed with or without a diet containing 3% or 6% DFAIII for 33 days or pair-fed control diet during the same period. Rats fed DFAIII showed significantly decreased food intake, energy intake, body weight gain, body energy accumulation, and fat tissue weight than control group, regardless of ovariectomy. DFAIII may decrease body fat dependent of reduced food/energy intake. Compared with the respective pair feeding groups, rats fed DFAIII showed significantly decreased body energy and fat tissue weight, regardless of ovariectomy, suggesting its potential as a low-energy substitute for high-energy sweeteners. The low energy of DFAIII may contribute to decreased body fat, which may not be dependent on obesity.
Identification of a novel acetylated form of branched-chain polyamine from a hyperthermophilic archaeon Thermococcus kodakarensis

Long/branched-chain polyamines are unique polycations found in thermophiles. The hyperthermophilic archaeon Thermococcus kodakarensis contains spermidine and a branched-chain polyamine, N4-bis(aminopropyl)spermidine, as major polyamines. The metabolic pathways associated with branched-chain polyamines remain unknown. Here, we used gas chromatography and liquid chromatography-tandem mass spectrometry analyses to identify a new acetylated polyamine, N4-bis(aminopropyl)-N1-acetylspermidine, from T. kodakarensis; this polyamine was not found in other micro-organisms. The amounts of branched-chain polyamine and its acetylated form increased with temperature, indicating that branched-chain polyamines are important for growth at higher temperatures. The amount of quaternary acetylated polyamine produced was associated with the amount of N4-bis(aminopropyl)spermidine in the cell. The ratio of acetylated to non-acetylated forms was higher in the stationary phase than in the logarithmic growth phase under high-temperature stress condition.
Inhibition of MMP‐3 or ‐9 suppresses lipopolysaccharide‐induced expression of proinflammatory cytokines and iNOS in microglia

Recently, matrix metalloproteinases (MMPs) are emerging as important molecules in neuroinflammation as well as neuronal cell death. However, the role of MMPs in activated microglia remains unclear. In the present study, we found that expressions of MMP‐1, ‐3, ‐8 and ‐9 were significantly induced by single or combined treatment of immunostimulants lipopolysaccharide (LPS) or phorbol myristate acetate (PMA) in primary cultured microglia and BV2 microglial cells. Inhibition of MMP‐3 or ‐9 significantly suppressed the expression of iNOS and pro‐inflammatory cytokines and the activities of NF‐κB, AP‐1, and MAPK in LPS‐stimulated microglia. The results suggest that MMP‐3 and ‐9 both mediate LPS‐induced inflammatory reactions. Inhibition of reactive oxygen species (ROS) by N‐acetyl‐cysteine or diphenylene iodonium significantly suppressed the expression of MMP‐3, MMP‐9, NO and TNF‐α in LPS‐stimulated microglia, suggesting that ROS is an early signaling inducer in LPS‐stimulated microglial cells. MMP inhibitors also suppressed ROS production, suggesting a cross‐talk between ROS and MMPs. Collectively, the present study demonstrates that MMP‐3 and MMP‐9 play a role as inflammatory mediators in activated microglia. Pharmacological intervention of MMPs especially MMP‐3 and ‐9 would be a therapeutic strategy for the treatment of inflammatory diseases in the CNS caused by over‐activation of microglial cells.
Targets for ethanol action and antagonism in Loop 2 of the extracellular domain of glycine receptors

The present studies used increased atmospheric pressure in place of a traditional pharmacological antagonist to probe the molecular sites and mechanisms of ethanol action in glycine receptors (GlyRs). Based on previous studies, we tested the hypothesis that physical–chemical properties at position 52 in extracellular domain Loop 2 of α1GlyRs, or the homologous α2GlyR position 59, determine sensitivity to ethanol and pressure antagonism of ethanol. Pressure antagonized ethanol in α1GlyRs that contain a non‐polar residue at position 52, but did not antagonize ethanol in receptors with a polar residue at this position. Ethanol sensitivity in receptors with polar substitutions at position 52 was significantly lower than GlyRs with non‐polar residues at this position. The α2T59A mutation switched sensitivity to ethanol and pressure antagonism in the WTα2GlyR, thereby making it α1‐like. Collectively, these findings indicate that (i) polarity at position 52 plays a key role in determining sensitivity to ethanol and pressure antagonism of ethanol; (ii) the extracellular domain in α1‐ and α2GlyRs is a target for ethanol action and antagonism and (iii) there is structural‐functional homology across subunits in Loop 2 of GlyRs with respect to their roles in determining sensitivity to ethanol and pressure antagonism of ethanol. These findings should help in the development of pharmacological agents that antagonize ethanol.
TWO EPIDEMICS OF WHOOPING COUGH IN FINLAND 1976–1977; age and vaccination of the patients, DPT vaccination rate in children in the epidemic areas, home exposure attack rates and symptomless bacteria carriers.

During a whooping cough epidemic in the region of Alavus and Töysä in 1976–1977 Bordetella pertussis strains were isolated from 51/121 (42%) patients showing symptoms of respiratory tract infection. Of these patients, 49 were children and two were adults. Among the children 42/49 (86%) were of school‐age. Vaccination was incomplete in 46 children. Of the children in this region 2.1% were unvaccinated. Basic DPT vaccination was incomplete in 6.2% and booster vaccination was lacking in 73.7% of children±4 years of age.
Pre‐conditioning induced by carbon monoxide provides neuronal protection against apoptosis

Carbon monoxide (CO) is an endogenous product of mammalian cells generated by heme‐oxygenase, presenting anti‐apoptotic properties in several tissues. The present work demonstrates the ability of small amounts of exogenous CO to prevent neuronal apoptosis induced by excitotoxicity and oxidative stress in mice primary culture of cerebellar granule cells. Additionally, our data show that endogenous CO is a heme‐oxygenase product critical for its anti‐apoptotic activity. Despite being neuroprotective, CO also induces reactive oxygen species generation in neurons. These two phenomena suggest that CO induces pre‐conditioning (PC) to prevent cell death. The role of several PC mediators, namely soluble guanylyl cyclase, nitric oxide (NO) synthase, and ATP‐dependent mitochondrial K channel (mitoKATP) was addressed. Inhibition of soluble guanylyl cyclase or NO synthase activity, or closing of mitoKATP abolishes the protective effect conferred by CO. In addition, CO treatment triggers cGMP and NO production in neurons. Opening of mitoKATP, which appears to be critical for CO prevention of apoptosis, might be a later event. We also demonstrated that reactive oxygen species generation and de novo protein synthesis are necessary for CO PC effect and neuroprotection. In conclusion, CO induces PC and prevents neuronal apoptosis, therefore constituting a novel and promising candidate for neuroprotective therapies.
Pharmacokinetics of factors IX, recombinant human activated factor VII and factor XIII

Summary. There is now a volume of literature on the pharmacokinetics (PK) of coagulation factor concentrates, although the majority is on factor VIII (FVIII) and factor IX (FIX). PK of FIX and FVIII are different with FIX having a larger volume of distribution (Vdss), higher elimination clearance (CL), longer mean resident time (MRT) and longer terminal half‐life (T1/2,β). Factor IX in vivo recovery (IVR) is also much shorter possibly due to reversible binding of FIX to the endothelium and possibly to platelets. There is considerable FIX PK variability between products (particularly between plasma‐derived FIX and recombinant FIX), and between individuals. Important inter‐individual factors leading to PK variability include age and body weight because plasma volume as a fraction of body weight decreases with increasing weight and hence age. Thus, IVR increases with body weight and hence age and is consequently lower in children than in adults. Absolute Vdss and CL increase linearly with body weight and age in children and adolescents, becoming stable in adults with more stable weight. Inter‐individual variability also likely applies to other clotting factors, particularly to recombinant activated FVII (rFVIIa) but likely also to the less well studied factor XIII (FXIII). The former is known to have an extremely short T1/2,β, large Vdss, high CL, short MRT, whereas the latter has an extremely long T1/2,β, large Vdss, short CL and long MRT. Both are discussed in this article. Understanding of PK of specific clotting factors in individual patients is important in order to make decisions regarding appropriate dosage and dosage intervals to treat patients, and to allow by means of computer modelling the determination of dosage to achieve target trough level at various dosing intervals for patients undergoing prophylaxis.