Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparison of four different peptides to enhance accumulation of liposomes into the brain

The cell penetrating peptide TAT, which appears to enter cells with alacrity, can pass through the BBB efficiently. It has been indentified to enhance the brain delivery of the liposome. However, little was known about its mechanism. TAT contains a basic region consisting of six arginine and two lysine residues. These eight basic amino acids seem to be the key to its highly efficient membrane translocation and brain delivery. In this study, four selected peptides are synthesized. (1) TAT peptide with terminal Cysteine (Cys-AYGRKKRRQRRR). (2) TAT peptide with disordered sequence (Cys-RKARYRGRKRQR). (3) Glycine and glutamic acid substituted TAT peptide (Cys-AYGGQQGGQGGG). (4) R8 (Cys-RRRRRRRR). Liposomes were chosen as the delivery vehicle. The peptide was covalently bonded with the liposome. We compare four peptides for their brain targeting potential, and investigate their ability to target liposomes to the brain in vitro and in vivo. The cellular uptake of these four liposomes by brain capillary endothelial cells (BCECs) of rats and C6s and the mechanism of the pathway of endocytosis were explored. Biodistribution in vivo was also investigated qualitatively and quantitatively. The results showed that the charge of the peptide played an important role in enhancing its brain delivery. The sequence had little to do with its membrane translocation and brain delivery indicated there might be no specific receptor or transporter for the Tat peptide.
Graded versus Intermittent Exercise Effects on Lymphocytes in Chronic Fatigue Syndrome.

PURPOSE There is increasing evidence of immune system dysfunction in chronic fatigue syndrome (CFS), but little is known of the regular exercise effects on immune cell parameters. This pilot study investigated the effects of graded and intermittent exercise on CD4 lymphocyte subset counts and activation compared with usual care. METHODS Twenty-four CFS patients (50.2 ± 10 yr) were randomized to graded exercise (GE), intermittent exercise (IE), or usual care (UC) groups; 18 sedentary non-CFS participants (50.6 ± 10 yr) were controls (CTL) for blood and immunological comparisons. Outcome measures were pre- and postintervention flow cytometric analyses of circulating lymphocyte subset cell counts; expression of CD3, CD4, CD25, and CD134; full blood counts; and V˙O2peak. RESULTS Preintervention, CD3 cell counts, and expression of CD4, CD25, CD134, and CD4CD25CD134 were significantly lower in GE, IE, and UC compared with CTL (P < 0.05). Total lymphocyte concentration was significantly lower in GE and IE groups compared with CTL. There were significant postintervention increases in i) expression of CD4 and CD4CD25CD134 for GE and IE, but CD25 and CD134 for IE only; ii) circulating counts of CD3 and CD4 for GE, and CD3, CD4, CD8, CD3CD4CD8, CD3CD16CD56, CD19, and CD45 for IE; iii) neutrophil concentration for GE; and iv) V˙O2peak and elapsed test time for IE and GE, V˙Epeak for IE. CONCLUSIONS Twelve weeks of GE and IE training significantly improved CD4 lymphocyte activation and aerobic capacity without exacerbating CFS symptoms. IE may be a more effective exercise modality with regard to enhanced CD4 activation in CFS patients.
Small beer? peer-to-peer lending in the craft beer sector

The recent surge in use of alternative sources of entrepreneurial finance is viewed as transformative, providing entrepreneurs with an increased variety of resourcing options. Through exploring cognitive heuristics of entrepreneurs’ financing decisions, this study examines provision of disintermediated debt through online platforms. Heretofore unexamined demand side issues reveal valuable processual advantages for entrepreneurs, along with ancillary non-financial benefits. Our study reveals the multifaceted nature of the financing decision, and how alternative finance is compatible with long standing entrepreneurial preferences for control and managerial independence. Peer to peer lending overcomes a number of issues relating to agency, networks, and spatial aspects of financing. Contrary to previous research, we find that marketing and promotion, rather than raising finance, are of greater importance. Entrepreneurs’ preferences for locally provided equity finance have implications for investors and platforms, and disintermediation of finance presents challenges to traditional funders. The surge in use of alternative finance varies by and within sectors, although it is important not to overstate its revolutionizing potential. Rather, it provides entrepreneurs with an expanded variety of financing options, and complements rather than replaces traditional sources. It is likely more beneficial in countries lacking diversification in private debt and equity markets.
Temporal delays in blind identification of primary somatosensory cortex

Blind source separation (BSS) is an emerging statistical and data processing technique which aims to recover unobservable source signals from the observed mixtures. Second-order blind identification (SOBI) is one BSS algorithm that relies on stationary second-order statistics based on joint diagonalization of a set of covariance matrices. In simulations, the use of multiple covariance matrices computed with different time delays, /spl tau/s, was beneficial for source separation, particularly when the underlying sources had highly overlapping spectra. Given the spectral overlap between actual brain sources, we experimented with different sets of temporal delays to empirically determine their effects on the isolation of electrical signals arising from a temporally and spatially well characterized brain location, the primary somatosensory cortex (SI). Using EEG data collected during median nerve stimulation, we found that the successful isolation of left and right SI activity required the use of a range of time delays and that the best separation was observed when the largest range of /spl tau/s from 1 up to 300 ms was used.
Toxicological Evaluation of Lung Responses After Intratracheal Exposure to Non-Dispersed Titanium Dioxide Nanorods

Fine- and coarse-sized titanium dioxide (TiO2) particles are considered to be relatively inert when inhaled. The goal of this study was to assess potential lung toxicity associated with well-characterized, non-dispersed rutile TiO2 nanorods (10 × 40 nm). In vitro bioreactivity of TiO2 nanorods was determined by electron spin resonance (ESR) to measure free radical production. To assess pulmonary effects in vivo, Sprague-Dawley rats were intratracheally instilled with saline, silica, or TiO2 nanorods (10 μg, 100 μg, or 1 mg/rat). On d 1, 3, and 6 posttreatment, left lungs were preserved for microscopy and histopathology, and lung lavage was performed on right lungs. Additional rats were treated with saline or TiO2 nanorods (100 μg or 1 mg/rat) on d 0, intratracheally inoculated with 5 × 105 Listeria monocytogenes on d 3, and bacterial clearance was assessed. ESR showed a significant concentration-dependent generation of hydroxyl radicals by TiO2 nanorods in the presence and absence of macrophages; however, the hydroxyl radical signals from TiO2 samples were low compared to silica. Rats exposed to 1 mg of TiO2 nanorods had significantly elevated levels of lung injury, inflammation, and lavage fluid monocyte chemoattractant protein (MCP)-1 and macrophage inflammatory protein (MIP)-2 on d 1 and 3 that subsided by d 6, unlike the silica response that persisted. Immune cytokine secretion in the lung and bacterial clearance were not affected by preexposure to TiO2 nanorods. To summarize, non-dispersed TiO2 nanorods were found to induce radical formation and cellular oxidant production, and to generate transient and reversible pneumotoxic effects, and to not markedly alter pulmonary immune function.
Hyperthermia exposure impaired the early stage of face recognition: An ERP study

We investigated the effect of hyperthermia exposure on the early stages of face processing by recording event-related potentials (ERPs) elicited by faces and non-face stimuli presented in upright and inverted orientations. Across all conditions, both the peak latencies of P1 and N170 components were earlier in the hyperthermia group than in the control participants. Although no effects of P1 amplitudes were influenced by hyperthermia, the face effect (larger amplitude for faces relative to other object categories) of the N170 was modulated by hyperthermia, whereas the face effect was significant in the control group, it was minimised in the hyperthermia group. The inversion effect of faces on N170 amplitudes, however, was not affected by hyperthermia. These data suggest that the detection of faces in the visual field and their initial streaming to face-specific structural encoding mechanisms are impaired by hyperthermia. However, subsequent face-specific configural processing revealed by the N170 inversion effect is not affected by hyperthermia. In addition, hyperthermia accelerates the early stage of visual perception, regardless of faces or non-face objects.
Paradoxical sleep insomnia and decreased cholinergic neurons after myocardial infarction in rats.

STUDY OBJECTIVES Acute myocardial infarction (MI) is followed, within a few hours, by neuronal loss in the central nervous system (CNS), including the limbic system, the hypothalamus, and the brainstem. Sleep before and after MI was investigated in the first experiment. In a parallel experiment, 2 weeks after MI, we quantified brainstem cholinergic neurons known to control paradoxical sleep (PS). MEASUREMENTS AND RESULTS Data were obtained from 28 adult male Sprague-Dawley rats weighing 350-375 g and maintained under a 12-12 light-dark cycle in 2 experiments on 16 and 12 rats, respectively. The 16 animals in the first experiment were implanted with chronic electroencephalographic (EEG) and electromyographic (EMG) electrodes. A week after surgery, these animals were habituated for 2 days to the recording equipment, and baseline sleep was charted for 24 h. The next morning, MI was induced in 8 rats by occluding the left anterior descending coronary artery for 40 min. The remaining 8 rats served as sham-operated controls. Sleep was recorded again 2 weeks after MI. The number of choline acetyltransferase (ChAT)-positive neurons was counted in the second, parallel experiment on 6 MI and 6 sham rats. Compared to the sham controls, MI rats displayed longer latency to sleep onset, shorter latency to paradoxical sleep (PS), and curtailed PS duration. The number of ChAT-positive neurons in the pedunculopontine tegmentum (PPT) area of MI rats was significantly decreased compared to the sham controls, while the number of laterodorsal tegmentum (LDT) cholinergic neurons was not different. CONCLUSION Acute MI is accompanied, within 2 weeks, by PS-specific insomnia that can be explained, at least partly, by a specific loss of cholinergic neurons in an area known to control PS.
Lethal arrhythmias in Tbx3-deficient mice reveal extreme dosage sensitivity of cardiac conduction system function and homeostasis

TBX3 is critical for human development: mutations in TBX3 cause congenital anomalies in patients with ulnar-mammary syndrome. Data from mice and humans suggest multiple roles for Tbx3 in development and function of the cardiac conduction system. The mechanisms underlying the functional development, maturation, and maintenance of the conduction system are not well understood. We tested the requirements for Tbx3 in these processes. We generated a unique series of Tbx3 hypomorphic and conditional mouse mutants with varying levels and locations of Tbx3 activity within the heart, and developed techniques for evaluating in vivo embryonic conduction system function. Disruption of Tbx3 function in different regions of the developing heart causes discrete phenotypes and lethal arrhythmias: sinus pauses and bradycardia indicate sinoatrial node dysfunction, whereas preexcitation and atrioventricular block reveal abnormalities in the atrioventricular junction. Surviving Tbx3 mutants are at increased risk for sudden death. Arrhythmias induced by knockdown of Tbx3 in adults reveal its requirement for conduction system homeostasis. Arrhythmias in Tbx3-deficient embryos are accompanied by disrupted expression of multiple ion channels despite preserved expression of previously described conduction system markers. These findings indicate that Tbx3 is required for the conduction system to establish and maintain its correct molecular identity and functional properties. In conclusion, Tbx3 is required for the functional development, maturation, and homeostasis of the conduction system in a highly dosage-sensitive manner. TBX3 and its regulatory targets merit investigation as candidates for human arrhythmias.
Variable antigen genes of the relapsing fever agent Borrelia hermsii are activated by promoter addition

Borrelia hermsii, an agent of replapsing fever, avoids the host's immune response by means of multiphasic antigenic variation. Serotype specificity is determined by variable antigens called the Vmp lipoproteins. Through recombination between linear plasmids a formerly silent vmp gene replaces another vmp gene at a telomeric expression locus. We examined strain HS1 borreliae before and after a switch from serotype 7 to serotype 21. The nucleotide sequences of 5 regions of silent and expressed vmp7 and vmp 21 were determined. Silent and active vmp 7 and vmp 21 genes shared a block of homologous sequences surrounding their 5′ ends. Sequences upstream of silent vmp 7 and vmp 21 genes lacked the promoter and substantially differed from each other. In this antigenic switch a vmp gene was activated by a recombination that placed it downstream of a promoter.
Intensive rehabilitation combined with HBO2 therapy in children with cerebral palsy: a controlled longitudinal study.

OBJECTIVE The present study aimed to assess the effect of intensive rehabilitation combined with hyperbaric oxygen (HBO2) therapy on gross motor function in children with cerebral palsy (CP). METHODS We carried out an open, observational, platform-independent study in 150 children with cerebral palsy with follow-up over eight months to compare the effects of standard intensive rehabilitation only (control group n = 20) to standard intensive rehabilitation combined with one of three different hyperbaric treatments. The three hyperbaric treatments used were: air (FiO2 = 21%) pressurized to 1.3 atmospheres absolute/atm abs (n = 40); 100% oxygen pressurized at 1.5 atm abs (n = 32); and 100% oxygen, pressurized at 1.75 atm abs (n = 58). Each subject assigned to a hyperbaric arm was treated one hour per day, six days per week during seven weeks (40 sessions). Gross motor function measure (GMFM) was evaluated before the treatments and at two, four, six and eight months after beginning the treatments. RESULTS All four groups showed improvements over the course of the treatments in the follow-up evaluations (p < 0.001). However, GMFM improvement in the three hyperbaric groups was significantly superior to the GMFM improvement in the control group (p < 0.001). There was no significant difference between the three hyperbaric groups. CONCLUSION The eight-month-long benefits we have observed with combined treatments vs. rehabilitation can only have been due to a beneficial effect of hyperbaric treatment.
Methicillin-susceptible Staphylococcus aureus ST398-t571 harbouring the macrolide-lincosamide-streptogramin B resistance gene erm(T) in Belgian hospitals.

OBJECTIVES Methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-susceptible S. aureus (MSSA), collected from 109 Belgian acute-care hospitals during a national survey in 2008, were investigated for macrolide-lincosamide (ML) resistance with particular emphasis on the analysis of erm(T)-carrying isolates. METHODS In total, 314 MRSA and 212 MSSA were collected and characterized by spa typing. The SCCmec type of MRSA was determined. Resistance to ML antibiotics was detected by agar dilution and resistant strains were screened by PCR for erm(A), erm(C) and msr(A). Five ML-resistant MSSA isolates, negative by PCR for the aforementioned genes, were further characterized. RESULTS Half of all MRSA isolates (n = 157; 50.0%) were resistant to erythromycin and harboured the gene erm(A) (n = 112), erm(C) (n = 41), erm(A) + erm(C) (n = 3) or msr(A) (n = 1). The erm(A) gene was mainly present in MRSA spa-CC002-ST5-SCCmec II and spa-CC008-ST8-SCCmec IV (where CC stands for clonal complex and ST stands for sequence type); the distribution of erm(C) was more diverse. Thirty-five of the 40 erythromycin-resistant MSSA (18.9%) carried the gene erm(A) (n = 17), erm(C) (n = 9) or msr(A) (n = 9). The remaining five MSSA were ST398-t571 isolates, which exhibited closely related ApaI PFGE patterns, harboured the gene erm(T) in the chromosomal DNA and did not exhibit additional resistances. These isolates were from severe infections in patients, of whom four had no contact and one had only indirect contact with livestock via a family member working in animal husbandry. CONCLUSIONS The ML-streptogramin B ('MLS(B)') resistance genes erm(A) or erm(C) were detected in the majority of ML-resistant MRSA and MSSA isolates. The erm(T) gene was identified in MSSA ST398 isolates from five independent patients who lacked direct contact with livestock.
Lipopolysaccharide activated phosphatidylcholine‐specific phospholipase C and induced IL‐8 and MCP‐1 production in vascular endothelial cells

Secretion of proinflammatory cytokines by lipopolysaccharide (LPS) activated vascular endothelial cells (VECs) contributes substantially to the pathogenesis of several inflammatory diseases such as atherosclerosis and septic shock. However, the mechanisms involved in this process are not well understood. Here, we investigated the role of phosphatidylcholine‐specific phospholipase C (PC‐PLC) in LPS‐induced IL‐8 and MCP‐1 production in VECs. The results showed that LPS elevated the level of PC‐PLC and the production of IL‐8 and MCP‐1 in Human umbilical vein vascular endothelial cells (HUVECs). Blocking the function of PC‐PLC by exploiting the neutralization antibody of PC‐PLC or tricyclodecan‐9‐yl‐xanthogenate (D609), an inhibitor of PC‐PLC, significantly inhibited LPS‐induced production of IL‐8 and MCP‐1 in HUVECs. Furthermore, the in vivo experimental results showed that the levels of PC‐PLC, IL‐8, and MCP‐1 in the aortic endothelium and serum were increased in mice injected with LPS. The increased levels of these molecules were also inhibited by the treatment with D609. The data suggested that blocking PC‐PLC function significantly inhibited LPS‐induced IL‐8 and MCP‐1 production in cultured HUVECs and in vivo. PC‐PLC might be a potential target for therapy in inflammation associated‐diseases such as atherosclerosis. J. Cell. Physiol. 226: 1694–1701, 2011. © 2010 Wiley‐Liss, Inc.
Purification of myristoylated and nonmyristoylated neuronal calcium sensor-1 using single-step hydrophobic interaction chromatography.

Neuronal calcium sensors (NCSs) belong to a family of Ca(2+)-binding proteins, which serve important functions in neurotransmission, and are highly conserved from yeast to humans. Overexpression of the neuronal calcium sensor-1, called frequenin in the fruit fly and in frog, increases the release of neurotransmitters. Studying the functional role of frequenin in mammals and understanding its structural dynamics is critically dependent on the availability of active purified protein. Neuronal calcium sensors like other members of the family share common structural features: they contain four EF-hands as potential binding sites for Ca(2+) and an N-terminal consensus sequence for myristoylation. Previously, recoverin, distantly related to NCSs, has been expressed and purified from Escherichia coli, involving a combination of different chromatographic steps. NCS-1 has earlier been purified adopting a two-step procedure used for recoverin purification. We have overexpressed NCS-1 from rat in its myristoylated and nonmyristoylated form in E. coli and purified it from crude lysates using a single-step hydrophobic interaction chromatography. The purified protein was identified by Western blotting and mass spectrometry and assayed for its ability to bind Ca(2+) using a Ca(2+) shift assay, terbium fluorescence, and Stains-all binding. The present protocol provides a rapid, more efficient and simplified, single-step method for purifying NCS-1 for structural and functional studies. This method can also be applied to purify related proteins of the superfamily.
Plasma oxidative stress biomarkers and progesterone profiles in a dairy cow diagnosed with an ovarian follicular cyst

This study was conducted to examine the oxidative stress biomarkers in a cow diagnosed with a follicular cyst in her left ovary. Progesterone (P4) and plasma oxidative stress status was measured in 13 Holstein cows after synchronization of oestrus with controlled internal drug release (CIDR) and prostaglandinF2α (PGF2α) protocol. The presence and size of ovarian structures were monitored by transrectal ultrasound at 4 hourly intervals. Of the 13 cows, 12 were monitored until ovulation was detected and recorded, whereas one cow failed to ovulate and developed a follicular cyst. Oxidative stress biomarkers; reactive oxygen metabolites (ROMs), biological antioxidant potential (BAP), oxidative stress index (OSI), glutathione (GSH), ceruloplasmin and advanced oxidation protein products (AOPP) were measured in the cystic cow and compared to those of the 12 ovulated cows and are referred to as higher or lower if they are outside the mean ± standard error of mean of those of ovulated cows. The cystic cow had lower ROMs and OSI between 36 and 84 h after PGF2α injection and at 9 h, from 36 to 60 h after PGF2α injection respectively. On the other hand, antioxidant (BAP and GSH) was higher in the cystic cow compared to her ovulated herd mates. The observed imbalance between oxidant and antioxidant might have disrupted the physiological events for ovulation to occur, leading to cystic ovarian disease.
Motives, choice of entry mode, and challenges of bank internationalization: Evidence from China

This study examines the motives, entry mode choice and challenges of the international expansion in an emerging country context. Data was collected via interviews from 30 senior managers based on a sample of 10 Chinese commercial banks (CCBs) involved in international expansion over the period of 2001-2013. This study finds that greenfield and mergers and acquisitions are the most popular foreign entry mode used by CCBs. The motives of emerging market banks’ internationalisation appear to be intrinsically linked to market development to serve customers operating in overseas market, government policies and strategic knowledge sourcing. In terms of challenges, the study finds lack of management resources/technical capacity, culture, adapting to the host country regulatory environment, and lack of experience to be the main challenges to bank internationalisation.