Miracle-dz/UniFAR-FTUs huggingface dataset:
Metabolic Engineering of Isoflavonoid Biosynthesis in Alfalfa1[w]

The potential health benefits of dietary isoflavones have generated considerable interest in engineering the synthesis of these phytoestrogens into plants. Genistein glucoside production (up to 50 nmol g−1 fresh weight) was engineered in alfalfa (Medicago sativa) leaves by constitutive expression of isoflavone synthase from Medicago truncatula (MtIFS1). Glucosides of biochanin A (4′-O-methylgenistein) and pratensein (3′-hydroxybiochanin A) also accumulated. Although MtIFS1 was highly expressed in all organs examined, genistein accumulation was limited to leaves. MtIFS1-expressing lines accumulated several additional isoflavones, including formononetin and daidzein, in response to UV-B or Phoma medicaginis, whereas the chalcone and flavanone precursors of these compounds accumulated in control lines. Enhanced accumulation of the phytoalexin medicarpin was observed in P. medicaginis-infected leaves of MtIFS1-expressing plants. Microarray profiling indicated that MtIFS1 expression does not significantly alter global gene expression in the leaves. Our results highlight some of the challenges associated with metabolic engineering of plant natural products, including tissue-specific accumulation, potential for further modification by endogenous enzyme activities (hydroxylation, methylation, and glycosylation), and the differential response of engineered plants to environmental factors.
Virtual autopsy with multiphase postmortem computed tomographic angiography versus traditional medical autopsy to investigate unexpected deaths of hospitalized patients: a cohort study.

BACKGROUND "Virtual" autopsy by postmortem computed tomography (PMCT) can replace medical autopsy to a certain extent but has limitations for cardiovascular diseases. These limitations might be overcome by adding multiphase PMCT angiography. OBJECTIVE To compare virtual autopsy by multiphase PMCT angiography with medical autopsy. DESIGN Prospective cohort study. (ClinicalTrials.gov: NCT01541995) SETTING: Single-center study at the University Medical Center Hamburg-Eppendorf, Hamburg, Germany, between 1 April 2012 and 31 March 2013. PATIENTS Hospitalized patients who died unexpectedly or within 48 hours of an event necessitating cardiopulmonary resuscitation. MEASUREMENTS Diagnoses from clinical records were compared with findings from both types of autopsy. New diagnoses identified by autopsy were classified as major or minor, depending on whether they would have altered clinical management. RESULTS Of 143 eligible patients, 50 (35%) had virtual and medical autopsy. Virtual autopsy confirmed 93% of all 336 diagnoses identified from antemortem medical records, and medical autopsy confirmed 80%. In addition, virtual and medical autopsy identified 16 new major and 238 new minor diagnoses. Seventy-three of the virtual autopsy diagnoses, including 32 cases of coronary artery stenosis, were identified solely by multiphase PMCT angiography. Of the 114 clinical diagnoses classified as cardiovascular, 110 were confirmed by virtual autopsy and 107 by medical autopsy. In 11 cases, multiphase PMCT angiography showed "unspecific filling defects," which were not reported by medical autopsy. LIMITATION These results come from a single center with concerted interest and expertise in postmortem imaging; further studies are thus needed for generalization. CONCLUSION In cases of unexpected death, the addition of multiphase PMCT angiography increases the value of virtual autopsy, making it a feasible alternative for quality control and identification of diagnoses traditionally made by medical autopsy. PRIMARY FUNDING SOURCE University Medical Center Hamburg-Eppendorf.
Non-AUG initiation codon and downstream inframe AUG in Pyrococcus Horikoshii: Evaluating two hypotheses

Non-AUG initiation codons in protein-coding genes in Pyrococcus horikoshii are associated with the presence of a downstream inframe AUG typically at the 4th codon, i.e., at the 9th nucleotide site when the 1st coding nucleotide is labeled 0. Here we report that the presence of this downstream codon depends not only on the presence/absence of the initiation AUG, but also on the strength of binding between the Shine-Dalgarno (SD) sequence in the 5'-UTR of mRNA and the anti-SD sequence in the 16S rRNA. Weak binding significantly increases the likelihood of having the downstream AUG. Genes with a GUG initiation codon have weaker binding and a high proportion of them have the downstream AUG. Deviation of the SD sequence from the optimal location also appears to increase the likelihood of the downstream AUG.
Nursing documentation prior to emergency admissions to the intensive care unit.

BACKGROUND Early identification of prodromal signs of acute deterioration of patients is essential in high quality care. Rigorous monitoring of patients is facilitated by risk assessment tools, e.g. the Modified Early Warning Score (MEWS). AIMS AND OBJECTIVES The purpose of the study was to estimate the accuracy of nursing documentation according to parameters that comprise MEWS in patients prior to emergency admission to the intensive care unit (ICU). METHODS The research design was retrospective and descriptive. Data was collected from medical records of in-patients who presented as emergency admission to two ICUs at a university hospital between 1 October and 31 December 2006. RESULTS Data was collected from 65 patients' records over the 3-month period. Most admissions occurred between the hours of 8 a.m. and 4 p.m. Respiratory failure was the primary reason for admission, followed by septic shock. Respiratory rate was documented for 14% of patients (n = 9) prior to ICU admission, which was the least documented observation. Urine output and fluid balance were documented for 40% of the patients, level of consciousness in 48% of patients (n = 31), temperature for 69% (n = 45) and oxygen saturation for 80% of the patients (n = 53). DISCUSSION Respiratory failure was the primary cause of emergency admission of in-patients to the ICUs with respiratory rate the least documented vital sign. Nursing documentation according to the MEWS was insufficient. CONCLUSIONS/RELEVANCE TO CLINICAL PRACTICE: Nurses need to be alerted to the necessity of documenting early signs of deterioration of patients, particularly the respiratory rate. With better monitoring and documentation of physiological parameters, emergency admission to the ICU might be avoided.
Interactions between glomerular mesangial cells, cytokines, and extracellular matrix.

This brief overview summarizes recent information on the interactions of glomerular mesangial cells (MC) with soluble cytokines and nonsoluble extracellular matrix (ECM). The presently available knowledge stems largely from glomerular cell culture studies and from experimental work with laboratory animals. ECM production by MC appears to be regulated primarily by the paracrine or autocrine effects of cytokines, such as interleukin 1, platelet-derived growth factor, and transforming growth factor beta. However, ECM itself also affects the behavior of cultured MC, e.g., with regard to cell replication and the production of ECM components and other proteins. At present, little is known about the recognition of ECM and cytokines by MC that allows these interactions to take place. First results indicate that MC, like other cell types, possess surface proteins belonging to the beta 1 integrin family, which serve as specific receptors for ECM molecules. Receptors for the cytokines platelet-derived growth factor, insulin-like growth factor 1, epidermal growth factor, and transforming growth factor beta have also been demonstrated on MC. The expression of various receptors on MC appears to be affected by the ECM substratum. Thus, it is becoming apparent that mesangial ECM is not only important as a mechanical scaffold of the glomerular capillary tuft but that it also contains and conveys information relevant for the regulation of the MC phenotype, e.g., by modulating the MC response to cytokines. The available evidence suggests that alterations of ECM composition in glomerular disease can directly or indirectly affect MC behavior, e.g., by promoting cell replication and further accumulation of ECM, eventually resulting in progressive mesangial and glomerular sclerosis.
Modification of the water oxidizing complex in leaves of the dgd1 mutant of Arabidopsis thaliana deficient in the galactolipid digalactosyldiacylglycerol.

The primary biochemical defect in the genetically well characterized dgd1 mutant of Arabidopsis thaliana causes a 90% reduction in the relative amount of the galactolipid digalactosyldiacylglycerol (DGDG). To study the effect of this DGDG deficiency on photosystem II (PS II), time-resolved transients of laser-flash-induced changes of the relative fluorescence quantum yield Fvar,rel(t) were measured in whole leaves from wild-type and the dgd1 mutant. The results obtained reveal (i) in untreated leaves the decay kinetics of Fvar, rel(t) reflecting QA. - reoxidation by endogenous plastoquinone are very similar in wild-type and the dgd1 mutant at room temperature, (ii) the Arrhenius plot of the temperature dependence of electron transfer from QA. - to QB exhibits a break point at about 19 degrees C in wild-type and about 12 degrees C in the dgd1 mutant, (iii) in leaves treated with DCMU the slow reoxidation of QA. - by the PS II donor side is blocked to a much higher extent in the dgd1 mutant (about 50%) compared to wild-type (about 10%), and iv) the normalized amplitude of Fvar,rel(t = 1 micros) reflecting the percentage of fast P680. + reduction by YZ exhibits a characteristic period four oscillation in wild-type while this feature is strongly damped in the dgd1 mutant. Presumably, the severe DGDG deficiency is causing the thermal down shift of a lipid phase transition that affects the QA. - reoxidation by QB. Most strikingly, the properties of the WOC are modified as a result of reduced DGDG content. Thus, the lipid DGDG appears to be of structural relevance for the WOC.
Cortical reorganization during recovery from complex regional pain syndrome

Objective: To characterize reorganization of the primary somatosensory cortex (S1) during healing process in complex regional pain syndrome (CRPS). Background: Recently, the authors showed extensive reorganization of the S1 cortex contralateral to the CRPS affected side. Predictors for these plastic changes were CRPS pain and the extent of mechanical hyperalgesia. It is unclear how these S1 changes develop following successful therapy. Methods: The authors used magnetic source imaging to explore changes in the cortical representation of digits (D) 1 and 5 in relation to the lower lip on the unaffected and affected CRPS side in 10 patients during a year or more of follow-up. Results: Cortical reorganization reversed coincident with clinical improvement. A reduction of CRPS pain correlated with recovery from cortical reorganization. Conclusions: Changes of the somatotopic map within the S1 cortex may depend on CRPS pain and its recovery.
Neurocognitive Deficits and Effects of Cognitive Reserve in Mild Cognitive Impairment

Background/Aims: Mild cognitive impairment (MCI) is a frequent syndrome in the older population, which involves an increased risk to develop Alzheimer's disease (AD). The latter can be modified by the cognitive reserve, which can be operationalized by the length of school education. MCI can be differentiated into four subtypes according to the cognitive domains involved: amnestic MCI, multiple-domain amnestic MCI, non-amnestic MCI and multiple-domain non-amnestic MCI. While neurocognitive deficits are a constituent of the diagnosis of these subtypes, the question of how they refer to the cognitive reserve still needs to be clarified. Methods: We examined neuropsychological deficits in healthy controls, patients with MCI and patients with mild AD (n = 485) derived from a memory clinic. To reduce the number of neuropsychological variables, a factor analysis with varimax rotation was calculated. In a second step, diagnostic groups including MCI subtypes were compared with respect to their clinical and neuropsychological characteristics including cognitive reserve. Results: Most MCI patients showed the amnestic multiple-domain subtype followed by the pure amnestic subtype, while the non-amnestic subtypes were rare. The amnestic subtype displayed a significantly higher level of cognitive reserve and higher MMSE scores than the amnestic multiple-domain subtype, which was in most cases characterized by additional psychomotor and executive deficits. Conclusions: These findings confirm earlier reports revealing that the amnestic multiple-domain subtype is the most frequent one and indicating that a high cognitive reserve may primarily prevent psychomotor and executive deficits in MCI.
Maternal low‐protein diet up‐regulates the neuropeptide Y system in visceral fat and leads to abdominal obesity and glucose intolerance in a sex‐ and time‐specific manner

Neuropeptide Y (NPY) mediates stress‐induced obesity in adult male mice by activating its Y2 receptor (Y2R) in visceral adipose tissue (VAT). Here, we studied whether the NPY‐Y2R system is also activated by maternal low‐protein diet (LPD) and linked to obesity in offspring. Prenatal LPD offspring had lower birth weights compared to normal‐protein diet (NPD) offspring. Female prenatal and lactation stress (PLS) offspring from mothers fed an LPD developed abdominal adiposity and glucose intolerance associated with a 5‐fold up‐regulation of NPY mRNA and a 6‐fold upregulation of Y2R mRNA specifically in VAT, in addition to elevated platelet‐rich‐plasma (PRP) NPY, compared to control females fed a high‐fat diet (HFD). Conversely, PLS male offspring showed lower NPY in PRP, a 10‐fold decrease of Y2R mRNA in VAT, lower adiposity, and improved glucose tolerance compared to control males. Interestingly, prenatal LPD offspring cross‐fostered to control lactating mothers had completely inverse metabolic and NPY phenotypes. Taken together, these findings suggested that maternal LPD activates the VAT NPY‐Y2R system and increases abdominal adiposity and glucose intolerance in a sex‐ and time‐specific fashion, suggesting that the peripheral NPY system is a potential mediator of programming for the offspring's vulnerability to obesity and metabolic syndrome. —Han, R. , Li, A. , Li, L. , Kitlinska, J. B. , Zukowska, Z. Maternal low‐protein diet up‐regulates the neuropeptide Y system in visceral fat and leads to abdominal obesity and glucose intolerance in a sex‐ and time‐specific manner. FASEB J. 26, 3528–3536 (2012). www.fasebj. org
Splicing-Independent Expression of the Herpes Simplex Virus Type 1 Thymidine Kinase Gene Is Mediated by Three cis-Acting RNA Subelements

ABSTRACT Herpes simplex virus genes are predominantly intronless. We identified cis-acting elements in the intronless herpes simplex virus type 1 thymidine kinase (TK) gene that facilitate intron-independent gene expression. TK sequences functionally replaced the hepatitis B virus (HBV) posttranscriptional regulatory element (PRE) by inducing the expression of the intronless HBV surface message. TK also activated the pDM138 assay by inducing the cytoplasmic accumulation of intron-containing RNA. Multiple cis-acting RNA sequences, or subelements, that induce cytoplasmic localization of unspliced RNA were mapped within the TK gene. The presence of multiple RNA subelements within the TK gene is reminiscent of the multiple subelements in the HBV PRE required for the cytoplasmic accumulation of intronless HBV RNAs. Similar to HBV PRE subelements, duplication of a single TK subelement resulted in greater-than-additive increases in activity. A reporter chimera containing a single TK subelement juxtaposed to an HBV PRE subelement demonstrated a commensurate increase in activity. These results suggest that viral intronless genes utilize a similar strategy for intron-independent gene expression that requires multiple cis-acting RNA signals. Furthermore, like HBV PRE-containing RNA, TK cytoplasmic localization is not sensitive to leptomycin B, a drug that inhibits the export of proteins containing nuclear export signals. From this, we conclude that proteins that bind TK and facilitate its cytoplasmic accumulation do not travel through a CRM1-dependent RNA transport pathway.
Impaired expression of genes regulating cholesterol efflux in human osteoarthritic chondrocytes

Altered lipid metabolism has been implicated as a critical player in osteoarthritis (OA). Our study aimed to investigate the expression of genes regulating cholesterol efflux in human chondrocytes and to study the effect of an LXR agonist on cholesterol efflux and lipid accumulation in osteoarthritic chondrocytes. ATP‐binding‐cassette transporter A1 (ABCA1), apolipoprotein A1 (ApoA1), and liver X receptors (LXRα and LXRβ) mRNA expression levels were evaluated using real‐time polymerase chain reaction (PCR) and ApoA1 protein levels by Western blot analysis in normal and osteoarthritic articular cartilage samples. Cholesterol efflux was evaluated in osteoarthritic chondrocytes radiolabeled with [1,2(n)‐3H] cholesterol after LXR treatment, while intracellular lipid accumulation was studied after Oil‐red‐O staining. Cholesterol efflux gene expressions were significantly lower in osteoarthritic cartilage compared to normal. Treatment of osteoarthritic chondrocytes with the LXR agonist TO‐901317 significantly increased ApoA1 and ABCA1 expression levels, as well as cholesterol efflux. Additionally, osteoarthritic chondrocytes presented intracellular lipids deposits, while no deposits were found after treatment with TO‐901317. Our findings suggest that impaired expression of genes regulating cholesterol efflux may be a critical player in osteoarthritis, while the ability of the LXR agonist to facilitate cholesterol efflux suggests that it may be a target for therapeutic intervention in osteoarthritis. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:1033–1039, 2010
Isobaric Ropivacaine 5 mg/mL for Spinal Anesthesia in Children

In this clinical trial, we evaluated the clinical effects of ropivacaine for spinal anesthesia in children. An open, prospective study was performed on 93 children, aged 1–17 yr, undergoing elective lower abdominal or lower limb surgery. A plain solution of ropivacaine 5 mg/mL at a dose of 0.5 mg/kg body weight (up to 20 mg) was administered via the L3-4 or L4-5 interspace with the patient in the lateral decubitus position. After injection, the patients were placed supine. The spread and duration of sensory analgesia and the degree of motor block were recorded. Satisfactory surgical anesthesia was achieved in 92 of the 93 children. Three children received general anesthesia; in one child spinal anesthesia failed, and in two cases surgery outlasted the duration of the sensory block. Four children received supplemental analgesia for skin incision. The mean highest level of sensory block was T6 (range, T2 to T12), and the mean time to the regression of sensory block to T10 was 96 min (range, 34–210 min). One child developed transient bradycardia and one hypotension. After discharge four children developed mild transient radiating neurologic symptoms and one epidural blood patch was performed for persistent position-dependent headache. We conclude that the block performance of intrathecal isobaric ropivacaine in children (>1 yr) is similar to that obtained in adults but the safety of the larger dose used in children warrants further studies.
Improvement of bone turnover markers and bone mineral density following treatment of primary aldosteronism.

BACKGROUND Recent studies showed association between hyperaldosteronism and low bone density among patients with primary aldosteronism (PA) due to secondary hyperparathyroidism. Our objective is to assess bone turnover markers (BTM) and bone mineral density (BMD) of PA patients compared to essential hypertension. METHODS This was an open-label, prospective, case-controlled study, conducted over 12 months. Fifty-two consecutive patients referred for secondary hypertension were screened. Eighteen patients with confirmed PA (diagnosis based on the Endocrine Society clinical guideline) and seventeen matched controls with essential hypertension were recruited. BTM (CTX and P1NP), BMD, intact parathyroid hormone (iPTH), and bone profile were assessed at baseline and three months following treatment among the PA patients. Calcium intake was assessed using a validated questionnaire. Primary outcomes were the changes of bone markers and BMD following treatment of PA, and their relation to other parameters. RESULTS PA patients had significantly lower serum calcium and higher iPTH despite comparable vitamin D levels with control group. Both BTM were significantly higher among the PA group. BMD of lumbar spine, neck of femur and distal radius did not differ between groups. Three months following treatment, there were significant: 1) reduction in BTM; 2) improvement in the lumbar spine BMD; 3) reduction in iPTH level; and 4) increment of serum 25-OH vitamin D level. CONCLUSIONS Our findings support that bone loss and potential fracture risk among PA patients are likely a result of aldosterone-mediated secondary hyperparathyroidism. Patients with early PA may already exhibit increased bone turnover despite no significant changes in BMD.
Edge adapted nonlinear multiscale transforms for compact image representation

We introduce nonlinear edge-adapted multiresolution transforms for image processing. These transforms have the same structure as wavelet basis decompositions, but incorporate a specific geometric treatment of edges, which results in sparser representations of piecewise smooth images and in turn better compression properties. We also observe visual improvements over classical wavelets for the compression of real images.
Preference and Awareness of Telemedicine in Primary Care Patients

Background The telemedicine services in Korea are expected to rapidly expand its use to the general population due to the development of digital networking, and its recent revision of related law and regulations. The purpose of this study was to investigate the knowledge and attitude of telemedicine in primary care patients. Methods We enrolled a total 243 participants, visited Family Medicine clinics and health promotion centers of university hospital in Seoul metrocity and Chungju city from April 1, 2010 to May 31, 2010. Data was collected by questionnaire, including demographic variables, knowledge and attitude of telemedicine. Results Among the total of 243 participants, 117 (49.8%) respondents were aware of telemedicine, and 178 (73.3%) respondents preferred telemedicine. The awareness showed differences according to the residence (P = 0.007), education (P = 0.03), and occupation (P = 0.02) of the respondents. The patient preference showed the differences at 50 years of age (P = 0.01) and in income of the participants (P = 0.005). Conclusion Awareness of telemedicine in primary care patients was low. As for the patients more than 50 years of age who will be having difficulty manipulating the instruments, more education is crucial. Establishment of appropriate plans to increase patient preference is needed, especially for patients with low-incomes.