Miracle-dz/UniFAR-FTUs huggingface dataset:
Mitochondrial DNA deletion in “identical” twin brothers

Defects of mitochondrial DNA (mtDNA) are an important cause of genetic disease in humans.1 The defect may take the form of a deletion or point mutation, and clinical features range from severe neonatal illness to mild muscle weakness later in life.2 In a recent epidemiology study, single large scale mtDNA deletion disorders represented approximately 25% of adult patients with mtDNA disease.3 The three main syndromes observed in these patients are Pearson’s syndrome (PS), a severe systemic illness of childhood associated with sideroblastic anaemia; Kearns-Sayre syndrome (KSS) which is also associated with multiple system involvement; and chronic progressive external ophthalmoplegia (CPEO) in which the predominant clinical problem relates to an eye movement disturbance and ptosis. In both KSS and PS the mtDNA deletion is present in many tissues,4–6 whereas in CPEO, the mtDNA deletion is found in muscle but not other tissues.5,7 In patients with single large scale mtDNA deletions, it is not established at which stage in development the mtDNA deletion occurs. For the vast majority of cases, there is no family history and as described above, the mtDNA deletion may be limited to a single tissue. Recently, we had the opportunity to study 31 year old twin brothers who were genetically identical in terms of nuclear markers, but one had developed CPEO whereas the other was completely asymptomatic. We hoped that by studying these brothers we might gain further insight into the origin of the mtDNA deletion. ### Case reports The twin brothers were born 2 months premature, and the first twin (the affected brother) required a forceps delivery. Although no specific problems were documented immediately after birth, the affected twin (patient 1) was noted to have a slightly asymmetric skull (probably related to the delivery) and a slight squint. He was, however, very athletic …
Brand loyalty for domestic and global brands: A case of Thai fast-moving consumer goods

The purpose of this research was to study potential differences in the formation of brand loyalty for domestic and global brands in Thai consumer groups through brand equity, consumer satisfaction, and country of origin effects. The study compared two well-known brands of a consumer product (shower gel), one of which presented as a local brand and the other of which had global branding. (Both brands are in fact manufactured by the same company and have similar functional and quality characteristics.) A convenience sample of Thai consumers (n = 400) was selected from shopping centers in and around Bangkok for a consumer survey about brand image and perceptions of the two brands. Factors in the formation of brand loyalty were then explored using structural equation modelling. The analysis showed that the effects of brand awareness and brand associations were similar for domestic and global brands. However, domestic brands had higher effects from customer satisfaction than perceived quality, while this relationship was reversed for global brands. The implication of this study is that domestic and global brands may be evaluated differently by consumers in some contexts, even if they are functional substitutes for each other. Consumers placed more emphasis on perceived quality than the brand experience for global brands. This could create problems for domestic brand marketers and those developing new domestic brands. However, this study only included a single product category. These results cannot be generalized across all consumer categories.
Critical Incident Exposure and Sleep Quality in Police Officers

Objective Police officers face many stressors that may negatively impact sleep quality. This study compares subjective sleep quality in police officers with that in control subjects not involved in police or emergency services. We examined the effects of critical incident exposure (trauma exposure) and routine (nontraumatic) work environment stressors on sleep quality after controlling for the effects of work shift schedule. Methods Subjective sleep disturbances were measured by the Pittsburgh Sleep Quality Index in police officers (variable-shift workers, N = 551; stable day-shift workers, N = 182) and peer-nominated comparison subjects (variable-shift workers, N = 98; stable day-shift workers, N = 232). The main predictor variables were 1) duty-related critical incident exposure to on-line policing and 2) work environment stress related to routine administrative and organizational aspects of police work. Results Police officers on both variable and stable day shifts reported significantly worse sleep quality and less average sleep time than the two corresponding control groups. Within police officers, cumulative critical incident exposure was associated with nightmares but only weakly associated with poor global sleep quality. In contrast, the stress from officers’ general work environment was strongly associated with poor global sleep quality. Sleep disturbances were strongly associated with posttraumatic stress symptoms and general psychopathology. Conclusions A large percentage of police officers report disturbances in subjective sleep quality. Although the life-threatening aspects of police work are related to nightmares, the routine stressors of police service seem to most affect global sleep quality in these subjects. These findings may have implications for health and occupational performance.
Designing a new generation of antidepressant drugs

Although longer‐term adaptive changes in receptor sensitivity may better explain the delayed onset of action of antidepressants, the mechanism based on acutely elevated noradrenaline (NA) and serotonin (5‐HT) synaptic levels remains the basis for new drug design. The dual action concept, which postulates that effects on both NA and 5‐HT are more advantageous than a selective action on serotonin reuptake (SSRI), has been used to design new antidepressants such as venlafaxine and mirtazapine. Both drugs enhance NA and 5‐HT neurotransmission with little affinity for receptors mediating tricyclic‐like side effects. Mirtazapine, the prototype noradrenergic and specific serotonergic antidepressant (NaSSA), specifically enhances 5‐HT, neurotransmission and blocks 5‐HT2 and 5‐HT3 receptors, and in contrast to venlafaxine lacks SSRI‐like and adverse cardiovascular side effects. The unique pharmacological action of mirtazapine is a result of implementation of two concepts: dual action as a basis of efficacy combined with receptor‐specific action as a basis of tolerability.
The Role of Culture, Language and Trade Agreements in Global Wine Trade

In the progressively globalising world, wine trade is changing shape. In recent decades, major wine producers have suffered a remarkable drop in their domestic wine consumption, while New World wine producers have increased their production potential and induced new demand in foreign markets. These changes have been accompanied by a geographical relocation of wine consumption and trade. The aim of our paper is to analyse the effect of cultural-geographical proximity, free trade and the role of linguistic similarity on bilateral wine trade in the world major wine producer countries, employing balanced panel gravity model. Regression results suggest that larger countries export more wine, while transport costs increase in line with geographical distance, especially for landlocked trading partners. Moreover, global wine export costs are lower if trading partners are culturally similar; have the same religion or both are members of the WTO or have regional trade agreements.
High‐throughput sequencing analysis of the chromosome 7q32 deletion reveals IRF5 as a potential tumour suppressor in splenic marginal‐zone lymphoma

Using high‐resolution genomic microarray analysis, a distinct genomic profile was defined in 114 samples from patients with splenic marginal zone lymphoma (SMZL). Deletion or uniparental disomy of chromosome 7q were detected in 42 of 114 (37%) SMZLs but in only nine of 170 (5%) mature B‐cell lymphomas (P < 0·00001). The presence of unmutated IGHV, genomic complexity, 17p13‐TP53 deletion and 8q‐MYC gain, but not 7q deletion, correlated with shorter overall survival of SMZL patients. Mapping studies narrowed down a commonly deleted region of 2·7 Mb in 7q32.1‐q32.2 spanning a region between the SND1 and COPG2 genes. High‐throughput sequencing analysis of the 7q32‐deleted segment did not identify biallelic deletions/insertions or clear pathogenic gene mutations, but detected six nucleotide changes in IRF5 (n = 2), TMEM209 (n = 2), CALU (n = 1) and ZC3HC1 (n = 1) not found in healthy individuals. Comparative expression analysis found a fourfold down‐regulation of IRF5 gene in lymphomas with 7q32 deletion versus non‐deleted tumours (P = 0·032). Ectopic expression of IRF5 in marginal‐zone lymphoma cells decreased proliferation and increased apoptosis in vitro, and impaired lymphoma development in vivo. These results show that cryptic deletions, insertions and/or point mutations inactivating genes within 7q32 are not common in SMZL, and suggest that IRF5 may be a haploinsufficient tumour suppressor in this lymphoma entity.
Proteolytic activation of protein kinase C delta by an ICE‐like protease in apoptotic cells.

These studies demonstrate that treatment of human U‐937 cells with ionizing radiation (IR) is associated with activation of a cytoplasmic myelin basic protein (MBP) kinase. Characterization of the kinase by gel filtration and in‐gel kinase assays support activation of a 40 kDa protein. Substrate and inhibitor studies further support the induction of protein kinase C (PKC)‐like activity. The results of N‐terminal amino acid sequencing of the purified protein demonstrate identity of the kinase with an internal region of PKC delta. Immunoblot analysis was used to confirm proteolytic cleavage of intact 78 kDa PKC delta in control cells to the 40 kDa C‐terminal fragment after IR exposure. The finding that both IR‐induced proteolytic activation of PKC delta and endonucleolytic DNA fragmentation are blocked by Bcl‐2 and Bcl‐xL supports an association with physiological cell death (PCD). Moreover, cleavage of PKC delta occurs adjacent to aspartic acid at a site (QDN) similar to that involved in proteolytic activation of interleukin‐1 beta converting enzyme (ICE). The specific tetrapeptide ICE inhibitor (YVAD) blocked both proteolytic activation of PKC delta and internucleosomal DNA fragmentation in IR‐treated cells. These findings demonstrate that PCD is associated with proteolytic activation of PKC delta by an ICE‐like protease.
Fundamental Research and Application of the Specific Fluidic Behavior of Mixed Solvents in a Microspace

The author herein reviews a specific microfluidic behavior exhibited by mixed-solvent solutions in a microspace, coined as the tube radial distribution phenomenon (TRDP). The specific fluidic behavior was observed in the following solution systems: ternary water-hydrophilic/hydrophobic organic solvents, water–surfactant, water-ionic liquid, and fluorous/ organic solvents. When the mixed homogeneous solutions were delivered into a microspace under certain conditions, the solvent molecules were radially distributed in the microspace, generating inner and outer phases with a kinetic liquid-liquid interface. The TRDP was fundamentally evaluated by fluorescence microscopy, phase diagrams construction, and the elution behaviors of solutes in a capillary tube. A TRDP-based capillary chromatography, referred to as tube radial distribution chromatography (TRDC), where the outer phase serves as a pseudo-stationary phase under laminar flow conditions, has been developed as one of the applications of TRDP. We have also investigated TRDP-based extraction, chemical reaction, and mixing processes, coined as tube radial distribution extraction (TRDE), tube radial distribution reaction (TRDR), and tube radial distribution mixing (TRDM), respectively. The concept and experimental findings regarding TRDP, TRDC, TRDE, TRDR, and TRDM are described in this review.
Investigating the Organizational and the Environmental Issues that Influence the Adoption of Healthcare Information Systems in Public Hospitals of Iraq

Healthcare information systems (HIS) are an important part of nowadays hospitals as it provides valuable benefits and functionalities for healthcare provision. However, the implementation and adoption of these complex innovations is a challenging task as documented by the literature; therefore, careful planning and consideration to all important factors that influence the adoption process by healthcare staff is required. Governmental reports stated that the usage of HIS systems within public hospitals of Iraq is still low and problematic; that’s why the current study aims at empirically investigating the opinions of healthcare staff regarding the adoption of HIS within public hospitals of Iraq. The current study extended the UTAUT model by integrating additional organizational and environmental factors and for that purpose a questionnaire was developed for obtaining the healthcare staff’s opinions. To the best of our knowledge, this is the first empirical study that utilized the UTAUT model to tackle the topic of HIS adoption in Iraq public healthcare sector. The study was able to explain 33% and 46% of the variance within the behavioral intention and the usage of HIS, respectively. The practical findings of this quantitative study can be helpful for healthcare officials to address the actual challenges related to HIS adoption and to set proper strategies for implementing futuristic HIS projects.
Functional adaptation of presynaptic chemokine receptors in EAE mouse central nervous system

In cortical synaptosomes of Experimental Autoimmune Encephalomyelitis (EAE) mice at the early stage of disease (13 days post immunization, d.p.i.), the Regulated upon Activation Normal T cell Expressed and Secreted (RANTES, CCL5)‐mediated control of [3H]D‐aspartate ([3H]D‐ASP) exocytosis elicited by a mild depolarizing stimulus (12 mM KCl) shifted from inhibition to facilitation. By using selective antagonists for the chemokine receptor (CCR) 1, 3, and 5 subtypes, we found that the pharmacological profile of the receptor(s) accounting for CCL5‐mediated effect was unaltered when compared to control. Inasmuch, CCR protein expression was unaltered. This studies was not extended at 21 d.p.i. since, at this stage, CCL5 failed to affect [3H]D‐ASP exocytosis. At 13 d.p.i. , the expression of CCR proteins was largely conserved when compared to control. In spinal cord synaptosomes of EAE mice at 21 d.p.i. , when presynaptic defects became evident, the [3H]D‐ASP exocytosis elicited by 15 mM KCl was significantly increased when compared to control and it was significantly potentiated by 1 nM CCL5. The antagonist pharmacological profile and the western blot analysis of the CCR proteins unveiled that the receptor repertoire involved was unmodified. Differently from controls, however, the CCR1 antagonist BX513 efficiently inhibited on its own [3H]D‐ASP exocytosis suggesting that this receptor could have adopted an active conformation. Altogether, our observations favor the use of CCR antagonists to the cure of neurological symptoms in patients suffering from demyelinating syndrome. Synapse 68:529–535, 2014. © 2014 Wiley Periodicals, Inc.
Which REE prediction equation should we use in normal-weight, overweight and obese women?

BACKGROUND & AIMS In our modern society, there is a growing and increasing prevalence of overweight, obesity and eating disorders and young female subjects frequently ask for nutritional counselling. Resting energy expenditure (REE) is essential to provide a sound diet to subjects seeking nutritional support. We perform a critical selection of accurate and reliable prediction equations employed on normal-weight, overweight and obese young women. METHODS REE of 157 young women of Caucasian race (18-35 years)was measured with indirect calorimetry and was compared with the principal prediction equations (Harris and Benedict, Owen, Mifflin, WHO, Bernstein and Robertson and Reid). The statistical analysis used to compare measured and the predicted REE was paired t -test, +/-95% confidence interval and Bland and Altman method. The influence of weight loss on the prediction error was estimated in 31 subjects. An additional REE measurement was performed on patients who had lost >or=5% of the initial body weight due to a sound low-calorie diet. RESULTS The equations more reliable in our study are Owen's equation in normal-weight subjects, Bernstein's equation in overweight subjects and Robertson and Reid's equation in obese subjects. Weight was a significant variable according to the stepwise regression analysis resulting in the following equation: 542.2 + 11.5 kg;R(2) : 0.59. Weight loss decisively increased the overestimation of the equations and only Owen's equation maintained the error of prediction within acceptable limits. CONCLUSIONS The equation of Owen in normal weight, Bernstein in overweight and of Robertson and Reid in obese subjects should be chosen when we have to predict REE in young women. Due to metabolic adaptation occurring during therapeutic or spontaneous energy restriction, we suggest to use Owen' s equation.
' s personal copy The Phosphatidylinositol 3-kinase ( PI 3 K ) inhibitor LY 294002 modulates cytokine expression in macrophages via p 50 nuclear factor kappa B inhibition , in a PI 3 K-independent mechanism

The Phosphatidylinositol 3-kinase (PI3K) inhibitor, LY294002 (LY2), has been previously reported to inhibit nuclear factor kB (NFkB) activity, in a PI3K-independent mechanism. The goals of the current research were to determine the specificity of LY2 regarding NFkB subunits, and to identify relevant modulation of cytokine expression in LPS-stimulated macrophages. We found that LY2 specifically diminished the level of p50, but not p65, NFkB in the nucleus of LPS-stimulated mouse RAW264.7 macrophages and human THP-1 monocytes. This activity of LY2 was mimicked by its PI3K-inert analog LY303511 (LY3), but not by another PI3K inhibitor – wortmannin. We further show that LY2 inhibited LPS-induced IL-10 expression by RAW264.7 macrophages, in a PI3K-independent mechanism. Moreover, using a deletion mutant of an IL-10 promoter reporter gene we demonstrate that the activity of the NFkB enhancer site at the IL-10 promoter is regulated by LY2 in a PI3K-independent manner. Finally, both LY2 and LY3 elevated TNFa production in the LPS tolerant state which is regulated by p50 NFkB homodimers, but not before tolerance development. The effects of LY2 and LY3 on p50 translocation and on cytokine production in LPS-stimulated macrophages are thus consistent with specific PI3K-independent inhibition of p50 NFkB homodimer activity by LY2. 2011 Elsevier Inc. All rights reserved. Abbreviations: LPS, lipopolysaccharide; TNFa, tumor necrosis factor alpha; IL-10, interleukin-10; PI3K, Phosphatidylinositol 3-kinase; LY2, LY294002; LY3, LY303511; NFkB, nuclear factor kB; Wort, wortmannin; PVDF, polyvinylidene fluoride; wed, wedelolactone; EMSA, electrophoretic mobility shift assay; ChIP, chromatin immunoprecipitation; DMEM, Dulbecco’s modified eagle’s medium. * Corresponding author. Tel. : +972 3 640 7192; fax: +972 3 640 7192. E-mail addresses: avnidorit@gmail.com (D. Avni), glucksam@post.tau. ac.il (Y. Glucksam), tsaffyz@tauex.tau. ac.il (T. Zor).
Comparison of different dietary amino acids as inducers of intestinal amino acid transport.

Intestinal amino acid (AA) transporters are known to be induced by raised levels of dietary protein or free AA mixtures, but little is known about whether certain AAs are more potent inducers than others. Hence we compared, in mouse jejunum, the inductive effects of seven different AAs (given to mice as dietary supplements) on the brush-border uptake of five solutes predominantly taken up via different transporters. The AAs tested as dietary supplements included one imino acid, two acidic AAs, two basic AAs, and two neutral AAs. The solutes whose uptakes we studied were D-glucose plus preferential substrates for the acidic AA, basic AA, neutral AA, and imino acid transporter. Mouse growth rates were consistently higher for dietary supplementation with nonessential than essential AAs, but there were no ration-related differences in intestinal morphometric parameters and almost none in active D-glucose uptake. AA transport is regulated independently of D-glucose transport. The four AA transporters are regulated semi-independently on each other: e.g., aspartate is a good inducer for only two of the four transporters, arginine for one or two, lysine for just one. Different AAs differ in their potencies at inducing the same AA transporter. In a few cases good substrates make good inducers (e.g., aspartate of the acidic AA transporter, valine of the neutral AA transporter). But often this is not true: the acidic AA aspartate is the best inducer of the basic AA transporter; the basic AA arginine but not lysine is a good inducer of the acidic AA transporter; and the imino acid proline is not a good inducer of the imino acid transporter. The adaptive significance of these discrepancies between inducers and transported substrates is unclear. Thus the differing dietary values of different AAs may be related to their differing values as inducers of AA transport, in addition to their well-known differing biosynthetic values as essential or nonessential nutrients.
Genome rearrangement and genetic instability in Streptomyces spp

compounds. Theseinclude numerous excreted hydrolytic enzymes, enzyme inhibitors, immunomodifiers, andover60% ofnaturally occurring antibiotics (5). Thegenome sizeis typically intherangeof5 x 103to7 x 103kilobases (kb) (19), whichissurprisingly large, being 1.5to2times thesize ofthatofEscherichia coli. Ithasa highG+C content of73 to75% (19)andsignificant levels ofbothrepetitive sequences(4to11%)and"foldback" DNA (2%). Thereisone majorgenetic linkage group whichtakestheformofa circular chromosome thatisfrequently present inmultiple copies per hyphalcompartment butispresent onlyas a single copy inthespores(25). Oneparticularly interesting aspect ofStreptomyces spp.is thephenomenon ofgenetic instability, whichmanifests itself asextraordinarily highmutation ratesaffecting certain species-specific traits. Unstable phenotypes areirreversibly lost atspontaneous frequencies ashigh as0.1%ofplated spores, butthese frequencies canbemadetoapproach 100%bythe use ofbothmutagenic (ethidium bromide andUV irradiation) andapparently nonmutagenic (cold storage) treatments (29). Themajority oftheseinstabilities are theresult of extensive chromosomal deletions which, interestingly, are frequently accompanied byintense DNA amplifications that takeplace intheabsence ofanyobvious selection pressure. Thedeletions can extend toinexcessof800kb(7), andthe physically linked amplified arrayscanextend to3,000 kb(20, 21),constituting 18and45%ofthechromosome, respectively. The lastdecadehasseen muchprogresstowards an understanding oftheseevents,reflecting theincreasing importance ofthegenus andthedevelopment ofefficient genetic systems(28) foritsmanipulation andexploitation. In thisminireview, we present an overview oftheinstability phenomenon andtheassociated chromosomal deletion and amplification events, withparticular reference toone ofthe best-characterized systems, S.glaucescens.