Miracle-dz/UniFAR-FTUs huggingface dataset:
Assessment of Usual Fruit, Vegetable and Vitamin C Intakes in a Sample of Egyptian Children: Pilot Study

The objective was to create an Egyptian database on the contributors of fruit and vegetables in the diets of preschool children and to estimate the usual daily intakes of fruits, vegetables and vitamin C. A total of 59 healthy boys and girls aged 2.5 - 6 years attending day care centers in urban Giza governorate completed the study by interviewing their mothers on 6x non-consecutive days using the 24 h dietary recall. Participants were classified according to age, gender and socioeconomic class. Prevalence of daily consumptions of fruits and vegetables amounted to 22% and 54%, respectively of the total children. The daily intakes of fruits and vegetables averaged 117.5 and 56.4 g, respectively. The consumption of different types of fruits and vegetables was unevenly distributed by different personal and social variables. Estimated daily vitamin C supply from the diet was 38 mg per child, which satisfied the respective recommended nutrient intake (RNI) of 30 mg for the first six years of life. However, the diet of 15% of the children covered less than 75% of RNI. Top fruits contributing to vitamin C were oranges, guava, watermelon, pears and grapes. Extra foods such as chipsy was consumed by 81% of the children, contributed 18% to daily vitamin C supply and also 58.6 mg sodium. A multilevel intervention strategy is warranted for promoting daily fruit and vegetable intake and healthy eating in early childhood.
Expression of the ORMDLS, Modulators of Serine Palmitoyltransferase, Is Regulated by Sphingolipids in Mammalian Cells*

Background: In contrast to their yeast orthologues, the mechanism by which mammalian ORMDLs regulate serine palmitoyltransferase is not understood. Results: Overexpression of serine palmitoyltransferase in HEK293 cells results in increased long-chain base synthesis and an activity-dependent increase in ORMDL expression. Conclusion: A product of ceramide synthase mediates regulation of ORMDL expression and inhibition of serine palmitoyltransferase. Significance: Serine palmitoyltransferase activity indirectly regulates ORMDL expression. The relationship between serine palmitoyltransferase (SPT) activity and ORMDL regulation of sphingolipid biosynthesis was investigated in mammalian HEK293 cells. Each of the three human ORMDLs reduced the increase in long-chain base synthesis seen after overexpression of wild-type SPT or SPT containing the C133W mutation in hLCB1, which produces the non-catabolizable sphingoid base, 1-deoxySa. ORMDL-dependent repression of sphingoid base synthesis occurred whether SPT was expressed as individual subunits or as a heterotrimeric single-chain SPT fusion protein. Overexpression of the single-chain SPT fusion protein under the control of a tetracycline-inducible promoter in stably transfected cells resulted in increased endogenous ORMDL expression. This increase was not transcriptional; there was no significant increase in any of the ORMDL mRNAs. Increased ORMDL protein expression required SPT activity since overexpression of a catalytically inactive SPT with a mutation in hLCB2a had little effect. Significantly, increased ORMDL expression was also blocked by myriocin inhibition of SPT as well as fumonisin inhibition of the ceramide synthases, suggesting that increased expression is a response to a metabolic signal. Moreover, blocking ORMDL induction with fumonisin treatment resulted in significantly greater increases in in vivo SPT activity than was seen when ORMDLs were allowed to increase, demonstrating the physiological significance of this response.
Decreasing Mitochondrial Fission Prevents Cholestatic Liver Injury*

Background: Bile acid-induced hepatocyte injury causes cholestatic liver disease. Results: Inhibiting mitochondrial fission prevents bile acid-induced hepatocyte death, and liver-specific decrease of mitochondrial fission in vivo limits bile duct ligation-induced liver injury and fibrosis. Conclusion: Controlling mitochondrial morphology is an effective strategy to decrease bile acid-induced liver injury. Significance: Mitochondrial fission is a new target to control cholestatic liver disease. Mitochondria frequently change their shape through fission and fusion in response to physiological stimuli as well as pathological insults. Disrupted mitochondrial morphology has been observed in cholestatic liver disease. However, the role of mitochondrial shape change in cholestasis is not defined. In this study, using in vitro and in vivo models of bile acid-induced liver injury, we investigated the contribution of mitochondrial morphology to the pathogenesis of cholestatic liver disease. We found that the toxic bile salt glycochenodeoxycholate (GCDC) rapidly fragmented mitochondria, both in primary mouse hepatocytes and in the bile transporter-expressing hepatic cell line McNtcp.24, leading to a significant increase in cell death. GCDC-induced mitochondrial fragmentation was associated with an increase in reactive oxygen species (ROS) levels. We found that preventing mitochondrial fragmentation in GCDC by inhibiting mitochondrial fission significantly decreased not only ROS levels but also cell death. We also induced cholestasis in mouse livers via common bile duct ligation. Using a transgenic mouse model inducibly expressing a dominant-negative fission mutant specifically in the liver, we demonstrated that decreasing mitochondrial fission substantially diminished ROS levels, liver injury, and fibrosis under cholestatic conditions. Taken together, our results provide new evidence that controlling mitochondrial fission is an effective strategy for ameliorating cholestatic liver injury.
Cystathionine β-Synthase (CBS) Domains Confer Multiple Forms of Mg2+-dependent Cooperativity to Family II Pyrophosphatases*

Background: Enzymes and transporters may contain regulatory nucleotide-binding cystathionine β-synthase domains. Results: Both substrate and adenine nucleotides bind cooperatively to four bacterial cystathionine β-synthase domain-containing pyrophosphatases. Conclusion: Cystathionine β-synthase domains internally inhibit catalysis and impart cooperativity; both effects are modulated by bound nucleotides. Significance: The observed regulatory complexity may be characteristic of cystathionine β-synthase domain-containing proteins involved in hereditary diseases. Regulated family II pyrophosphatases (CBS-PPases) contain a nucleotide-binding insert comprising a pair of cystathionine β-synthase (CBS) domains, termed a Bateman module. By binding with high affinity to the CBS domains, AMP and ADP usually inhibit the enzyme, whereas ATP activates it. Here, we demonstrate that AMP, ADP, and ATP bind in a positively cooperative manner to CBS-PPases from four bacteria: Desulfitobacterium hafniense, Clostridium novyi, Clostridium perfringens, and Eggerthella lenta. Enzyme interaction with substrate as characterized by the Michaelis constant (Km) also exhibited positive catalytic cooperativity that decreased in magnitude upon nucleotide binding. The degree of both types of cooperativity increased with increasing concentration of the cofactor Mg2+ except for the C. novyi PPase where Mg2+ produced the opposite effect on kinetic cooperativity. Further exceptions from these general rules were ADP binding to C. novyi PPase and AMP binding to E. lenta PPase, neither of which had any effect on activity. A genetically engineered deletion variant of D. hafniense PPase lacking the regulatory insert was fully active but differed from the wild-type enzyme in that it was insensitive to nucleotides and bound substrate non-cooperatively and with a smaller Km value. These results indicate that the regulatory insert acts as an internal inhibitor and confers dual positive cooperativity to CBS domain-containing PPases, making them highly sensitive regulators of the PPi level in response to the changes in cell energy status that control adenine nucleotide distribution. These regulatory features may be common among other CBS domain-containing proteins.
A Critical Role of the C-terminal Segment for Allosteric Inhibitor-induced Aberrant Multimerization of HIV-1 Integrase*

Background: Allosteric integrase (IN) inhibitors (ALLINIs) promote aberrant protein multimerization. Results: ALLINI-2 induces protein-protein interactions, including C-terminal residues Lys-264 and Lys-266, which lead to aberrant, higher-order IN multimerization. Conclusion: The protein-protein contacts beyond the inhibitor binding site contribute to aberrant IN multimerization. Significance: Our findings provide structural clues and underscore the significance for exploiting IN multimerization as a new therapeutic target. Allosteric HIV-1 integrase (IN) inhibitors (ALLINIs) are a promising class of antiretroviral agents for clinical development. Although ALLINIs promote aberrant IN multimerization and inhibit IN interaction with its cellular cofactor LEDGF/p75 with comparable potencies in vitro, their primary mechanism of action in infected cells is through inducing aberrant multimerization of IN. Crystal structures have shown that ALLINIs bind at the IN catalytic core domain dimer interface and bridge two interacting subunits. However, how these interactions promote higher-order protein multimerization is not clear. Here, we used mass spectrometry-based protein footprinting to monitor surface topology changes in full-length WT and the drug-resistant A128T mutant INs in the presence of ALLINI-2. These experiments have identified protein-protein interactions that extend beyond the direct inhibitor binding site and which lead to aberrant multimerization of WT but not A128T IN. Specifically, we demonstrate that C-terminal residues Lys-264 and Lys-266 play an important role in the inhibitor induced aberrant multimerization of the WT protein. Our findings provide structural clues for exploiting IN multimerization as a new, attractive therapeutic target and are expected to facilitate development of improved inhibitors.
Regulation of Selenocysteine Incorporation into the Selenium Transport Protein, Selenoprotein P*

Background: Selenocysteine incorporation into selenoprotein P (SEPP1), which contains 10 Sec residues, is unique. Results: Processive Sec incorporation can be reconstituted in vitro, independently of the conserved non-SECIS portions of the 3′-UTR. Conclusion: Processivity is intrinsic, but efficiency is governed by selenium levels. Significance: SEPP1 synthesis is essential for male fertility and proper neurologic function. Selenoproteins are unique as they contain selenium in their active site in the form of the 21st amino acid selenocysteine (Sec), which is encoded by an in-frame UGA stop codon. Sec incorporation requires both cis- and trans-acting factors, which are known to be sufficient for Sec incorporation in vitro, albeit with low efficiency. However, the abundance of the naturally occurring selenoprotein that contains 10 Sec residues (SEPP1) suggests that processive and efficient Sec incorporation occurs in vivo. Here, we set out to study native SEPP1 synthesis in vitro to identify factors that regulate processivity and efficiency. Deletion analysis of the long and conserved 3′-UTR has revealed that the incorporation of multiple Sec residues is inherently processive requiring only the SECIS elements but surprisingly responsive to the selenium concentration. We provide evidence that processive Sec incorporation is linked to selenium utilization and that reconstitution of known Sec incorporation factors in a wheat germ lysate does not permit multiple Sec incorporation events, thus suggesting a role for yet unidentified mammalian-specific processes or factors. The relationship between our findings and the channeling theory of translational efficiency is discussed.
Functional and structural brain changes in anti–N‐methyl‐D‐aspartate receptor encephalitis

Anti–N‐methyl‐D‐aspartate receptor (NMDAR) encephalitis is an autoimmune encephalitis with a characteristic neuropsychiatric syndrome and severe and prolonged clinical courses. In contrast, standard clinical magnetic resonance imaging (MRI) remains normal in the majority of patients. Here, we investigated structural and functional brain changes in a cohort of patients with anti‐NMDAR encephalitis.
Phospholipid Flippase Activities and Substrate Specificities of Human Type IV P-type ATPases Localized to the Plasma Membrane*

Background: The enzymatic activities of mammalian P4-ATPases are incompletely characterized. Results: ATP11A and ATP11C catalyze flipping of NBD-PS and NBD-PE, whereas ATP8B1 preferentially catalyzes flipping of NBD-PC. Furthermore, some PFIC1 mutants of ATP8B1 failed to flip PC. Conclusion: ATP11A/ATP11C and ATP8B1/ATP8B2 preferentially translocate aminophospholipids and PC, respectively. Significance: This is the first evidence showing that the PC-flipping activity of ATP8B1 is associated with the episode of PFIC1. Type IV P-type ATPases (P4-ATPases) are believed to translocate aminophospholipids from the exoplasmic to the cytoplasmic leaflets of cellular membranes. The yeast P4-ATPases, Drs2p and Dnf1p/Dnf2p, flip nitrobenzoxadiazole-labeled phosphatidylserine at the Golgi complex and nitrobenzoxadiazole-labeled phosphatidylcholine (PC) at the plasma membrane, respectively. However, the flippase activities and substrate specificities of mammalian P4-ATPases remain incompletely characterized. In this study, we established an assay for phospholipid flippase activities of plasma membrane-localized P4-ATPases using human cell lines stably expressing ATP8B1, ATP8B2, ATP11A, and ATP11C. We found that ATP11A and ATP11C have flippase activities toward phosphatidylserine and phosphatidylethanolamine but not PC or sphingomyelin. By contrast, ATPase-deficient mutants of ATP11A and ATP11C did not exhibit any flippase activity, indicating that these enzymes catalyze flipping in an ATPase-dependent manner. Furthermore, ATP8B1 and ATP8B2 exhibited preferential flippase activities toward PC. Some ATP8B1 mutants found in patients of progressive familial intrahepatic cholestasis type 1 (PFIC1), a severe liver disease caused by impaired bile flow, failed to translocate PC despite their delivery to the plasma membrane. Moreover, incorporation of PC mediated by ATP8B1 can be reversed by simultaneous expression of ABCB4, a PC floppase mutated in PFIC3 patients. Our findings elucidate the flippase activities and substrate specificities of plasma membrane-localized human P4-ATPases and suggest that phenotypes of some PFIC1 patients result from impairment of the PC flippase activity of ATP8B1.
Dysregulation of the Hypothalamus‐Pituitary‐Adrenal Axis in Male and Female, Genetically Obese (ob/ob) Mice

The autosomal, recessive obesity of ob/ob mice is associated with hypercorticosteronemia and amelioration of most symptoms of obesity following adrenalectomy. Increased adrenocorticotropic hormone (ACTH) secretion has been hypothesized on the basis of several reports of higher pituitary ACTH content in ob/ob mice compared to lean littermates. However, the only measurement of ACTH blood concentration found lower levels in ob/ob mice than in leans suggesting that hypercorticosteronemia might result solely from an enhanced adrenal response to ACTH and also suggesting that the ob/ob's elevated pituitary ACTH content might be due to decreased ACTH secretion rather than increased ACTH synthesis. In our study, basal serum ACTH levels were higher in ob/ob males and females compared to sex‐matched lean littermates. Anterior pituitary ACTH synthesis was also elevated as indicated by increased content of ACTH and proopiomelanocortin mRNA in obese mice of both sexes; however hypothalamic corticotropin‐releasing factor content was not different in lean and obese mice. Basal serum ACTH and corticosterone (CS) levels showed normal circadian rhythm in both phenotypes and sexes, but the circadian increase in CS level was much greater in obese mice than in leans despite equal serum ACTH increases in the two phenotypes. Ether stress at both peak and trough of the circadian rhythm also stimulated much larger serum CS increases in obese mice even though ACTH increases were again equal in the two phenotypes. Taken together, these results strongly indicate that ob/ob mice have increased synthesis and secretion of pituitary ACTH despite the presence of chronically elevated serum CS. This hyperactivity of the hypothalamo‐pituitary‐adrenal axis appears to be most pronounced in ob/ob females since pituitary ACTH content was equal in obese males and females despite much higher circulating CS levels in the females. Furthermore, the results also indicate an enhanced response to ACTH by the adrenal cortex of the obese mouse. Thus, ob/ob mice exhibit abnormal hypothalamo‐pituitary‐adrenal axis function with hyperactivity occurring at the level of pituitary ACTH synthesis/secretion as well as at the level of adrenocortical response to ACTH.
GABA(A) Receptor Pi (GABRP) Stimulates Basal-like Breast Cancer Cell Migration through Activation of Extracellular-regulated Kinase 1/2 (ERK1/2)*

Background: GABRP correlates with the basal-like breast cancer (BLBC)/triple negative subtype, but its function in this disease is poorly understood. Results: Silencing GABRP in BLBC cells decreases migration, BLBC-associated cytokeratins and ERK1/2 activation. Conclusion: A GABRP-ERK1/2-cytokeratin axis maintains BLBC migration. Significance: GABRP is a component of a cell-surface receptor, thus, targeting this signaling axis may have therapeutic potential in BLBC. Breast cancer is a heterogeneous disease comprised of distinct subtypes predictive of patient outcome. Tumors of the basal-like subtype have a poor prognosis due to inherent aggressiveness and the lack of targeted therapeutics. Basal-like tumors typically lack estrogen receptor-α, progesterone receptor and HER2/ERBB2, or in other words they are triple negative (TN). Continued evaluation of basal-like breast cancer (BLBC) biology is essential to identify novel therapeutic targets. Expression of the pi subunit of the GABA(A) receptor (GABRP) is associated with the BLBC/TN subtype, and herein, we reveal its expression also correlates with metastases to the brain and poorer patient outcome. GABRP expression in breast cancer cell lines also demonstrates a significant correlation with the basal-like subtype suggesting that GABRP functions in the initiation and/or progression of basal-like tumors. To address this postulate, we stably silenced GABRP in two BLBC cell lines, HCC1187 and HCC70 cells. Decreased GABRP reduces in vitro tumorigenic potential and migration concurrent with alterations in the cytoskeleton, specifically diminished cellular protrusions and expression of the BLBC-associated cytokeratins, KRT5, KRT6B, KRT14, and KRT17. Silencing GABRP also decreases phosphorylation of extracellular regulated kinase 1/2 (ERK1/2) in both cell lines and selective inhibition of ERK1/2 similarly decreases the basal-like cytokeratins as well as migration. Combined, these data reveal a GABRP-ERK1/2-cytokeratin axis that maintains the migratory phenotype of basal-like breast cancer. GABRP is a component of a cell surface receptor, thus, these findings suggest that targeting this new signaling axis may have therapeutic potential in BLBC.
Health-Related Quality of Life of Patients with Chronic Depression in Malaysia

Objective: To evaluate the health-related quality of life (HRQOL) of patients with chronic depression. Methods: The study involved patients with chronic depression being followed-up at an outpatient clinic at a local hospital in Malaysia. HRQOL was assessed using the Sheehan Disability Scale (SDS); while symptom severity was assessed using the Montgomery-Asberg Depression Rating Scale (MADRS). Results: 104 patients of Malay, Chinese and Indian ethnic groups met the selection criteria. Mean total SDS and MADRS scores was 9.36 ± 7.92 and 13.99 ± 11.58 respectively. There were no significant differences of HRQOL scores between the different ethnicities and between males and females. Symptom severity significantly influenced total and component HRQOL scores. Conclusions: The HRQOL of patients with chronic depression was found to be significantly influenced by symptom severity. Data obtained in this study can be used in the design and implementation of therapeutic and preventive interventions. Please click PDF below to download the full paper.
Losartan prevents acquired epilepsy via TGF‐β signaling suppression

Acquired epilepsy is frequently associated with structural lesions after trauma, stroke, and infections. Although seizures are often difficult to treat, there is no clinically applicable strategy to prevent the development of epilepsy in patients at risk. We have recently shown that vascular injury is associated with activation of albumin‐mediated transforming growth factor β (TGF‐β) signaling, and followed by local inflammatory response and epileptiform activity ex vivo. Here we investigated albumin‐mediated TGF‐β signaling and tested the efficacy of blocking the TGF‐β pathway in preventing epilepsy.
Nonconvulsive seizures in subarachnoid hemorrhage link inflammation and outcome

Nonconvulsive seizures (NCSz) are frequent following acute brain injury and have been implicated as a cause of secondary brain injury, but mechanisms that cause NCSz are controversial. Proinflammatory states are common after many brain injuries, and inflammation‐mediated changes in blood–brain barrier permeability have been experimentally linked to seizures.
Seroprevalence of autoantibodies against brain antigens in health and disease

We previously reported an unexpectedly high seroprevalence (∼10%) of N‐methyl‐D‐aspartate‐receptor subunit‐NR1 (NMDAR1) autoantibodies (AB) in healthy and neuropsychiatrically ill subjects (N = 2,817). This finding challenges an unambiguous causal relationship of serum AB with brain disease. To test whether similar results would be obtained for other brain antigen‐directed AB previously connected with pathological conditions, we systematically screened serum samples of 4,236 individuals.
Determinants of food choice among adults in an urban community: A highlight on risk perception

Purpose – This study was conducted to explore the underlying reasons of food choice and the association with risk perception in an urban community. The paper aims to discuss these issues.Design/methodology/approach – Using a cross‐sectional design, adults between 20 and 60 years old, selected by convenience sampling from three different races; Malay, Chinese and Indian, in Sungai Petani, Kedah were surveyed. A self‐administered food choice questionnaire was used and data collected were analysed using SPSS Statistic 17.0. Findings – Religion, risk perception and sensory appeal were the most prominent factors affecting food choice of respondents. Age showed significant correlation with mood and sensory appeal. Monthly income was significantly correlated with convenience, weight control and familiarity. Risk perception was found to be correlated with all motives except familiarity and religion.Research limitations/implications – A larger sample with approximately equal number of respondents from the various r.
A peek behind the curtain: Peer review and editorial decision making at Stroke

The mechanisms of peer review and editorial decision making often appear opaque to junior academic neurologists, especially those who have not yet published many papers or served as journal referees themselves. Previous entries in the NeuroGenesis career development series from the Editor‐in‐Chief have reviewed some of the reasons why faculty should participate as peer reviewers when given the opportunity and the factors that authors should consider in choosing appropriate journals for their own manuscripts. In this article, Sposato et al present the results of a systematic analysis of the editorial process at a leading neurology subspecialty journal; their findings will be of interest to readers at all stages of their careers who seek a better understanding of what goes on “behind the scenes” in journal decisions. — Bernard Chang, MD, NeuroGenesis Editor