Miracle-dz/UniFAR-FTUs huggingface dataset:
Brain‐targeted co‐delivery of β‐amyloid converting enzyme 1 shRNA and epigallocatechin‐3‐gallate by multifunctional nanocarriers for Alzheimer's disease treatment

Progressive memory loss and cognitive dysfunction are hallmark clinical features of Alzheimer's disease (AD). As a possible treatment for AD, we developed an epigallocatechin‐3‐gallate (EGCG) and β‐site amyloid precursor protein (APP) cleaving enzyme 1 antisense (BACE1‐AS) shRNA‐encoded plasmid. The plasmid was loaded on to RVG29 peptide‐targeted multifunctional nanoparticles (NPs) (REGS‐PN). The polymeric NPs were characterized by flow cytometry, biocompatibility assay, pharmacokinetic analysis, Western blot analysis, and the Morris water maze (MWM) test. The differences in plasma and brain NP accumulation following intravenous administration showed a significantly longer circulation time for EGS‐PN and REGS‐PN in the blood stream. In contrast, free EGCG was rapidly eliminated from the circulation. REGS‐PM successfully travelled through the blood–brain barrier and was present at a higher concentration in the brain compared with both non‐targeted NPs and free EGCG. REGS‐PN administration to APPswe/PS1dE9 double transgenic mice (APP/PS1 mice) resulted in downregulation of the key enzyme in amyloid‐β formation (BACE1) and amyloid beta, indicating synergistic therapeutic activity. The MWM test revealed that simultaneous delivery of a therapeutic gene and EGCG (REGS‐PN) remarkably improved the spatial learning and memory capabilities of APP/PS1 mice as well as wild type mice compared with the free EGCG‐treated group. With these results, we propose that co‐delivery of a therapeutic gene (shRNA) and EGCG in a multifunctional nanocarrier could achieve higher therapeutic concentrations in the brain and could be an excellent strategy for AD treatment.
Mutations in exon 3 of the β-catenin gene are rare in melanoma cell lines

Mutations in exon 3 of the CTNNB1 gene encoding β-catenin have been reported in colorectal cancer cell lines and tumours. Although one study reported mutations or deletions affecting β-catenin in 20% of melanoma cell lines, subsequent reports detected a much lower frequency of aberrations in uncultured melanomas. To determine whether this difference in mutation frequency reflected an in vitro culturing artefact, exon 3 of CTNNB1 was screened in a panel of 62 melanoma cell lines. In addition, reverse transcription-polymerase chain reaction (RT-PCR) was performed to detect intragenic deletions affecting exon 3. One out of 62 (1.6%) cell lines was found to carry a mutation, indicating that aberration of the Wnt-1/wingless pathway through activation of β-catenin is a rare event, even in melanoma cell lines.
Extensive Distribution of Galanin-Immunoreactive Neuronal Systems in a Fresh Water Snail, Indoplanorbis exustus, and Partial Coexistence with Choline Acetyltransferase-Iike Immunoreactivity

Abstract Immunohistochemical techniques were employed to investigate the distribution of galanin-like immunoreactivity in the central nervous system (CNS) of the snail, Indoplanorbis exustus, and immunoreactivity with an antibody against choline acetyltransferase (CAT) in galanin-immunoreactive somata was also examined. Galanin-immunoreactive (Gal-IR) cells were observed in all ganglia. They were classified into large (50 &mgr;m), medium (21 &mgr;m), and small (13 &mgr;m)-sized neurons and small Gal-IR cells dominated over large and medium Gal-IR cells in number. Gal-IR cells were most abundant in the cerebral ganglion. Several immunoreactive somata were seen in the parietal, visceral, and pedal ganglia, and only a few Gal-IR cells in the pleural and buccal ganglia. Densely arranged Gal-IR fiber bundles were observed in the cerebro-pleural, parieto-pleural and bucco-cerebral connectives. Of the peripheral nerves, the pallial and pharyngeal nerves contained more numerous Gal-IR fibers than other peripheral nerves. By Western blot analysis, the galanin antibody detected approximately 6.1 kDa band, suggesting a pre-form or a long form of galanin. Some GalIR cells in the cerebral ganglion and a few in the pleural and parietal ganglia were also immunoreactive for CAT. These results indicate that a distinct neuronal system with galanin or galanin-like peptide is present in the CNS of the snail, and suggest that a part of the galanin neuronal system is cholinergic. The peptide may function as a neurotransmitter/neuromodulator and/or neurohormone in the snail.
Recent trends in antipsychotic polypharmacy in the treatment of schizophrenia

Ichihashi et al reported that 43% of patients had antipsychotic polypharmacy. Number of antipsychotics used in patients with schizophrenia in Japan was the greatest among Asian countries. However, the antipsychotic polypharmacy rate in Japan decreased gradually. Recent systematic review, meta‐analysis and meta‐regression analysis demonstrated that antipsychotic augmentation was superior to monotherapy. However, several cohort studies have suggested a significant association between antipsychotic daily dose and mortality. In addition, most pharmacokinetic interactions with antipsychotics occur at the metabolic level and usually involve changes in the activity of the major drug‐metabolizing enzymes involved in their biotransformation. Thus, avoidance of unnecessary polypharmacy, knowledge of the interaction profiles of individual agents, and careful individualization of dosage based on close evaluation of clinical response and possibly plasma drug concentrations are essential to prevent and minimize potentially adverse drug interactions in patients receiving antipsychotics.
[Clinical effect of propranolol in the treatment of respiratory hemangioma in infants and young children].

OBJECTIVE To study the clinical effect of oral propranolol in the treatment of respiratory hemangioma in infants and young children. METHODS A retrospective analysis was performed from the chart review data of children with respiratory hemangioma treated by oral propranolol and diagnosed by bronchoscopy and laryngeal plain enhanced CT/MRI from November 2012 to December 2019. RESULTS A total of 20 children were enrolled. All children had improvement in the symptoms of laryngeal stridor and dyspnea after oral administration of propranolol for 1-2 days. The median treatment time was 10 months (range 6-12 months). The median follow-up time was 10 months (range 3-15 months). Of the 20 children, 19 (95%) achieved regression of tumor, and 1 (5%) experienced an increase in tumor size during reexamination at 6 months after drug withdrawal and had no recurrence after the treatment with an increased dose of propranolol for 6 months. Only 1 child (5%) had adverse reactions, and 1 child (5%) was still under treatment. CONCLUSIONS Oral propranolol can quickly relieve the symptoms such as dyspnea and achieve tumor regression, with few adverse events, and it is therefore an effective method for the treatment of respiratory hemangioma in infants and young children.
Statistical Survey of the Blind in New Jersey

T H E New Jersey State Commission for the Blind, which has been in active existence since 1910, has had in voluminous case folders, in home teachers' records, and the like, a mass of material about the blind and visually handicapped persons it has served and is serving. The members of the staff, however, were handicapped in making practical use of this material because the data about the entire case load, or the individual case, were not readily available in summarized form. There was no analysis available to which the Commission could turn if it wanted to study its service program in relation to the needs of those on the register as revealed by their present ages and past and present occupations. The Commission's prevention program, for instance, would have more talking points if it could point to the fact that 27 per cent of the blindness in New Jersey was caused by accidents and could detail the types of injuries caused by the industrial and non-industrial accidents. Follow-up work on the success of children who had been to residential schools for the blind could be facilitated if it were possible to find easily which individuals, over a period of years, had had the opportunity of special study. Owing to the varied activities of the Commission, it was extremely difficult to find out how many persons on the register had not been visited in a given year, or in two years---eases that the overworked home teachers perhaps had not been able to reach. It was impossible without reading through the folders, some of which were very thick, to get a picture of the individual blind person, the history of his blindness, his needs and advantages, and the services which the Commission had rendered him over a period of years. This situation, frequently found in state commissions for the blind, was inevitable because the limited permanent clerical staff was too crowded with current work to set up the necessary tools, the card record and reporting system. The New Jersey Commission had, however, long recognized that such a system would improve the work from the administrative point of view and permit adequate planning for the future, would reveal any weaknesses in the work as a whole and deficiencies in the program of certain individuals, and at the same time would give a real picture of the services the Commission renders.
Egr2-guided histone H2B monoubiquitination is required for peripheral nervous system myelination

Abstract Schwann cells are the nerve ensheathing cells of the peripheral nervous system. Absence, loss and malfunction of Schwann cells or their myelin sheaths lead to peripheral neuropathies such as Charcot-Marie-Tooth disease in humans. During Schwann cell development and myelination chromatin is dramatically modified. However, impact and functional relevance of these modifications are poorly understood. Here, we analyzed histone H2B monoubiquitination as one such chromatin modification by conditionally deleting the Rnf40 subunit of the responsible E3 ligase in mice. Rnf40-deficient Schwann cells were arrested immediately before myelination or generated abnormally thin, unstable myelin, resulting in a peripheral neuropathy characterized by hypomyelination and progressive axonal degeneration. By combining sequencing techniques with functional studies we show that H2B monoubiquitination does not influence global gene expression patterns, but instead ensures selective high expression of myelin and lipid biosynthesis genes and proper repression of immaturity genes. This requires the specific recruitment of the Rnf40-containing E3 ligase by Egr2, the central transcriptional regulator of peripheral myelination, to its target genes. Our study identifies histone ubiquitination as essential for Schwann cell myelination and unravels new disease-relevant links between chromatin modifications and transcription factors in the underlying regulatory network.
FREE RADICAL SCAVENGING ACTIVITY OF ARTEMISIA VULGARIS, L. LEAF EXTRACTS

Free radicals and Reactive Oxygen Species (ROS) are byproducts arising from numerous physiological and biochemical processes. The over-production of ROS can lead to damage to cellular biomolecules like lipids, DNA and proteins, which is implicated in the development of many pathological conditions including cancer, hypertension, diabetes and atherosclerosis. The deleterious effects of ROS are removed by the presence of compounds called antioxidants. The plant species acts as an excellent source of antioxidants, one among them is Artemisia vulgaris. The main objective of the present work was to study the free radical scavenging effects of Artemisia vulgaris leaf extracts (aqueous, methanol & chloroform). The result evident that the plant extracts possesses the effect to scavenge the battery of free radicals (DPPH, ABTS, superoxide, nitric oxide, hydroxyl radicals and hydrogen peroxide) tested, among all the three extracts used, the methanolic extract exhibited maximum effect compared to aqueous and chloroform extracts.
Hydraulic control of stomatal conductance in Douglas fir [Pseudotsuga menziesii (Mirb.) Franco] and alder [Alnus rubra (Bong)] seedlings

Experiments were conducted on 1-year-old Douglas fir [Pseudotsuga menziesii (Mirb.) Franco] and 2- to 3-month-old alder [Alnus rubra (Bong)] seedlings growing in drying soils to determine the relative influence of root and leaf water status on stomatal conductance (g c ). The water status of shoots was manipulated independently of that of the roots using a pressure chamber that enclosed the root system. Pressurizing the chamber increases the turgor of cells in the shoot but not in the roots. Seedling shoots were enclosed in a whole-plant cuvette and transpiration and net photosynthesis rates measured continuously. In both species, stomatal closure in response to soil drying was progressively reversed with increasing pressurization. Responses occurred within minutes of pressurization and measurements almost immediately returned to pre-pressurization levels when the pressure was released. Even in wet soils there was a significant increase in g c with pressurization. In Douglas fir, the stomatal response to pressurization was the same for seedlings grown in dry soils for up to 120d as for those subjected to drought stress over 40 to 60 d. The stomatal conductance of both Douglas fir and alder seedlings was less sensitive to root chamber pressure at higher vapour pressure deficits (D), and stomatal closure in response to increasing D from 1.04 to 2.06 kPa was only partially reversed by pressurization. Our results are in contrast to those of other studies on herbaceous species, even though we followed the same experimental approach. They suggest that it is not always appropriate to invoke a 'feedforward' model of short-term stomatal response to soil drying, whereby chemical messengers from the roots bring about stomatal closure.
SEPARATING SIZE FROM ALLOMETRY: ANALYSIS OF LOWER JAW MORPHOLOGY IN THE FOX SQUIRREL, SCIURUS NIGER

Abstract The fundamentals of mechanics provide a strong basis for the hypothesis that allometry could be an important constraint on evolutionary changes in shape. Empirical evidence that allometry accounts for sufficient shape variation to be an effective constraint is much weaker. Numerous studies claim to show that most shape variation is correlated with size, but nearly all these studies use morphometric methods that confound size and shape. Consequently, the proportion of the shape variation correlated with size remains unknown. To address this issue, I examined ontogenetic change and adult variation in lower jaws of the fox squirrel, Sciurus niger. Jaw morphologies were quantified using traditional distance measurements and geometric shape variables computed from landmark coordinates. The same analyses were performed on each data set. As expected, analyses of the distance measurements found that allometry accounted for nearly all ontogenetic variation. The same analysis on the coordinate data found that allometry accounts for <50% of the ontogenetic variation in shape. In analyses of adults, allometry explained >50% of the variation in distance measurements but <25% of the variation in shape. These results confirm that analyses of distance measurements confound size and shape and that this can lead to erroneous claims about the importance of allometry.
Arabidopsis thaliana VDAC2 involvement in salt stress response pathway

Soil salinity seriously affects plants distribution and yield, while salt stress induces SOS genes, and voltage-dependent anion channels (VDAC) and a mitochondrial porin, are induced too. In this paper, phenotypes of AtVDAC2 transgenic lines and wild type (RLD) were analyzed. It was found that AtVDAC2 over-expressing transgenic plants were more sensitive to NaCl, and produced more H 2 O 2 in the NaCl treatment. Also, to find the inner reason, the salt overly sensitive gene 3 (SOS3) expression level was changed with the expression of AtVDAC2. So, it was conjectured that the signal of salt stress response was first sent to AtVDAC2, then AtVDAC2 expression improved, leading to the down-stream signals changes, such as accumulation of H 2 O 2 and improved expression of SOS3. So, it was found that in the over-expression of transgenic lines with AtVDAC2 up-regulation, SOS3 expression increased significantly, and in the inhibited-expressing lines, it was vice versa. In summary, AtVDAC2 was involved in salt stress signaling pathway, and it regulated SOS3 gene expression. Key words: Arabidopsis thaliana, voltage-dependent anion channels (VDAC), salt stress, signaling pathway.
Factors Affecting the Distribution of the Leopard Cat Prionailurus bengalensis on East Asian Islands

Abstract. Members of the Felidae, being found at the top of the trophic hierarchy in an ecosystem, usually require extremely large habitat ranges. Thus, most cat species are found only on continents or large islands. The leopard cat Prionailurus bengalensis, the most widespread species of East Asian cat, is an exception to this rule, occurring on several small islands as well as larger islands and the Asian continent. Using published data for 38 East Asian islands, I evaluated the effects of geographical and biological factors on the persistence of the leopard cat population on an island by using regression analyses. The results suggested that the probability of existence of this cat species on an island increased with increasing species richness of potential prey, or with decreasing species richness of potential competitors. Geographical variation in the feeding habits of the leopard cat was also examined to clarify its ecological adaptation to different environments. The leopard cat chiefly preys on rodents but occasionally also feeds on other kinds of animals depending on region. On small islands with a small number of carnivore species, the cat frequently feeds on non-mammalian prey. This suggests that the cat potentially utilizes a variety of food items. The diet width of the leopard cat may be being determined by availability of prey items and intensity of interspecific competition.
GEOGRAPHIC LIMITS AND LOCAL ZONATION: THE BARNACLES SEMIBALANUS (BALANUS) AND CHTHAMALUS

The interactions between the intertidal barnacles Semiba! anus (Ba/anus) ba! anoides and Chthama! usfragilis were examined in order to determine whether the factors which influence local zonation in the intertidal also contribute to the estab lishment of geographic limits. Both physical and biotic factors influence intertidal zonation at the northern limit of Chthamalus in New England. On sloping surfaces Semibalanus died at all shore levels higher than mid tide level, apparently as a result ofdesiccation associated with high summer temperatures. Chthamalus settlement occurred at all shore levels above mean tide level, and postsettlement mortality apparently restricts Chthama! us to high shore locations where Semibalanus growth and survival is inhibited. North of the northern limit of Chthamalus, Semibalanus does not suffer summer heat death, so it occupies the zone where Chthamalus would have a refuge from corn petition further south. The northern limit of Chthamalus is set not by factors directly related to cold acting on Chthamalus. Rather the northern limit appears to be set by cold which allows the dominant competitor to exclude Chthamalus from its refuge zone. South of the northern limit the competitor, Semiba! anus, is excluded from the high shore by high summer temperatures.
DESIGNING OF ELISA KIT FOR DIAGNOSIS OF ANTI-TOXOPLASMA SPECIFIC IGG, USING EXERTED/SECRETED ANTIGENS AND ITS DIAGNOSIS POTENCY

هدیکچ هقباــ س فدــ ه و : سیزومسلاپوســ کوت صیخشــ ت تــ هج جــ یار شور (Toxoplasmosis) یــ یعت یــ تنآ ن هــ یلع یداــ ب کمک هب مرس رد امسلاپوسکوت نومزآ یم یژولورس یاه دشاب . رد یلبق تاعلاطم یتنآ زا نژ یعفد یاه ـب یحـشرت ه تـسد تشک طیحم رد لگنا تشک زا هدمآ RPMI هدافتـسا تـسا هدـش . رد نـیا هـعلاطم ، کـچوک شوـم قافـص عیاـم رد لـگنا داد تشـک یهاگشیامزآ دـش ه نژ یـتنآ زا و یاـه هـب صیخشـت یازـیلا تـیک یـحارط رد نژ یـتنآ ناوـنع هـب هدـمآ تـسد یتنآ یداب یاه هدافتسا امسلاپوسکوت دض دش . شور و داوم اه : هک یهاگشیامزآ کچوک دیفس شوم قافص عیام 3 یکات اب یقافص لخاد قیرزت قیرط هب لبق زور تیئوز لاپوسکوت یاه س دوب هدش هدولآ ام ، و دش هدیشک نازیم هب g × 750 هب تدم 15 هقیقد ویفیرتناس ژ دیدرگ . بوسر سپس عابشا موینومآ تافلوس ) 40 دصرد ( یواح بیکرت ناونع هب و هیهت نآ ییور عیام زا E/SA هگن بسانم طیارش رد دش یراد . هنومن زا هدافتسا اب یناسنا مرس یاه بابسا (kit) ازیلا ) میدار IgG ایلاتیا روشک تخاس ( هنومن و شیامزآ و یفنم یاه یواح
Higher venlafaxine serum concentrations necessary for clinical improvement? Time to re-evaluate the therapeutic reference range of venlafaxine

Background: The therapeutic reference range for venlafaxine in antidepressant treatment has been defined as 100 to 400 ng/mL. However, in an everyday setting active moiety concentrations above the therapeutic reference range were often reported. Aim: The aim of this study was to re-evaluate the therapeutic reference range of venlafaxine. Methods: In-patients (⩽60 years) with major depressive episodes receiving antidepressant monotherapy with venlafaxine during routine clinical treatment were included in this observational study. Depressive symptom severity was evaluated on a weekly basis using the Hamilton Depression Rating Scale (HAMD-21), and therapeutic drug monitoring analyses were performed. Resting electrocardiograms were analyzed in week 3, week 5 and week 7 of study participation. Results: Clinical improvement from baseline to week 4 was significantly associated with increasing serum concentrations of the active moiety of venlafaxine (N = 23, Pearson correlation, p = 0.009), but not with the dose of venlafaxine. Patients achieving remission showed significantly higher serum concentrations than patients achieving response/non-response (Kruskal–Wallis test, p = 0.019). Moreover, in patients with serum concentrations above 400 ng/mL time to remission and time to response was significantly shorter than in patients with concentrations below 400 ng/mL (Mantel–COX test, p = 0.001; p = 0.010). QTc time was below the upper limit of a normal QTc time (450 ms) for all patients. Conclusion: The serum concentration of the active moiety and not the dose determined the effect of venlafaxine. Shorter remission times without ECG alterations in patients with serum concentrations above the therapeutic reference range suggest a re-evaluation of the therapeutic reference range for venlafaxine in larger studies.
Balancing growth and adaptation to stress: crosstalk between brassinosteroid and abscisic acid signaling.

Plant growth and development are plastic and can adapt to environmental changes. In this process different plant hormones coordinate to modulate plant growth and environmental interactions. In this article, we describe the individual brassinosteroid (BR) and abscisic acid (ABA) signaling pathways, emphasize the specific regulatory mechanisms between ABA and BR responses and discuss how both phytohormones coordinate growth, development and stress responses in plants. BR signaling is essential for plant development, while ABA signaling is activated to ensure plants survive stress. The crosstalk between BR and ABA, especially protein phosphorylation, protein stability control and downstream transcription control of key components of both pathways are discussed in terms of modulating plant development and stress adaptation. This article is protected by copyright. All rights reserved.