Miracle-dz/UniFAR-FTUs huggingface dataset:
Crystal structure of the global regulator FlhD from Escherichia coli at 1.8 Å resolution

FlhD is a 13.3 kDa transcriptional activator protein of flagellar genes and a global regulator. FlhD activates the transcription of class II operons in the flagellar regulon when complexed with a second protein FlhC (21.5 kDa). FlhD also regulates other expression systems in Escherichia coli. We are seeking to understand this plasticity of FlhD's DNA‐binding specificity and, to this end, we have determined the crystal structure of the isolated FlhD protein. The structure was solved by substituting seleno‐methionine for natural sulphur‐methionine in FlhD, crystallizing the protein and determining the structure factor phases by the method of multiple‐energy anomalous dispersion (MAD). The FlhD protein is dimeric. The dimer is tightly coupled, with an intimate contact surface, implying that the dimer does not easily dissociate. The FlhD monomer is predominantly α‐helical. The C‐termini of both FlhD monomers (residues 83–116) are completely disrupted by crystal packing, implying that this region of FlhD is highly flexible. However, part of the C‐terminus structure in chain A (residues 83–98) was modelled using a native FlhD crystal. What is seen in chain A suggests a classic DNA‐binding, helix–turn–helix (HTH) motif. FlhD does not bind DNA by itself, so it may be that the DNA‐binding HTH motif becomes rigidly defined only when FlhD forms a complex with some other protein, such as FlhC. If this were true, it might explain how FlhD exhibits plasticity in its DNA‐binding specificity, as each partner protein with which it forms a complex could allosterically affect the binding specificity of its HTH motif. A disulphide bridge is seen between the unique cysteine residues (Cys‐65) of FlhD native homodimers. Alanine substitution at Cys‐65 does not affect FlhD transcription activator activity, suggesting that the disulphide bond is not necessary for either dimer stability or this function of FlhD. Electrostatic potential analysis indicates that dimeric FlhD has a negatively charged surface.
Shared susceptibility for celiac disease and inflammatory bowel disease?

We read with interest the study by Leeds et al. assessing the relationship between celiac disease and inflammatory bowel disease (1). In their investigation, they found an increased prevalence of inflammatory bowel disease among celiac disease patients. Interestingly, a recent report suggested that celiac disease and ulcerative colitis might share common genetic risk factors involving tight junction-mediated barrier defects of the bowel (2). Inspired by these facts, we wanted to conduct a large Scandinavian population-based study to test if there is evidence for co-occurrence of celiac disease, inflammatory bowel disease and other autoimmune disorders. We took advantage of an existing large Scandinavian population-based database which has been described previously(3–5). Briefly, the database includes all lymphoma patients (n=41,179) diagnosed in Sweden (1958–1998) and Denmark (1968–1997); 93,781 population-based controls; and all their linkable first-degree blood relatives (n=371,043) (3–5). Thus, a total of 506,003 individuals were included in the database. Through record-linkage with the nationwide inpatient registers in Sweden and Denmark, we captured hospital-discharge record data regarding celiac disease and a wide range of 32 other autoimmune and related disorders (4). For lymphoma patients, we restricted the information on celiac disease and other autoimmune disorders to one year prior to the date of lymphoma diagnosis. We used Chi-square statistics to test if celiac disease patients had excess co-occurrence of inflammatory bowel disease and other autoimmune disorders. In our study, we were able to confirm and extend the results by Leeds et al. (1). First, we defined a total of 253 individuals (prevalence rate ~1 per 2,000) with a hospital-discharge diagnosis of celiac disease. Second, when evaluating the co-occurrence of celiac disease and other autoimmune disorders, we found persons with (versus without) celiac disease to have a higher frequency of ulcerative colitis (n=8, p<0.0001) as well as Crohn’s disease (n=6, p<0.0001). Also, based on small numbers, we found co-occurrence for other autoimmune conditions (Table 1). TABLE 1 Co-occurring hospital-discharge diagnoses of celiac disease and other autoimmune disorders among 506,003 individuals in Scandinavia In summary, in this study based on over half a million individuals, we found 253 persons with a hospital-discharge diagnosis of celiac disease. Using a large Scandinavian population-based database, among individuals affected with celiac disease we observed significant co-occurrence of both ulcerative colitis and Crohn’s disease, which confirms and expands the clinical-based observations by Leeds et al (1). Our findings support the theory that there might be a shared susceptibility for celiac disease and inflammatory bowel disease (2). Alternatively, one might conjecture that celiac disease, in some cases, could be a precursor state of a subsequent inflammatory bowel disease (1). Future work is needed to better define underlying mechanism of these findings.
Risk factors for anastomotic leak following colorectal surgery: a case-control study.

OBJECTIVE To assess anastomotic leak (AL) risk factors in a large patient series. DESIGN Case-control study. SETTING The Mount Sinai Hospital. PATIENTS Ninety patients with AL following colorectal resection and 180 patients who underwent uncomplicated procedures. MAIN OUTCOME MEASURES Risk factors associated with development of AL. RESULTS The AL rate was 2.6%. Five risk factors for AL were identified: (1) preoperative albumin level lower than 3.5 g/dL (odds ratio [OR] 2.8; 95% confidence interval [CI], 1.3-5.1) (P = .03); (2) operative time of 200 minutes or longer (OR, 3.4; 95% CI, 2.0-5.8) (P = .01); (3) intraoperative blood loss of 200 mL or more (OR, 3.1; 95% CI, 1.9-5.3) (P = .01); (4) intraoperative transfusion requirement (OR, 2.3; 95% CI, 1.2-4.5) (P = .02); and (5) histologic specimen margin involvement in disease process in patients with inflammatory bowel disease (IBD) (OR, 2.9; 95% CI, 1.4-6.1) (P = .01). Patients with all 3 intraoperative risk factors had an OR of 22.1; 95% CI, 2.8-175.4 (P < .001) for development of AL. CONCLUSIONS Histologic resection margin involvement in disease process in patients with IBD, preoperative albumin levels lower than 3.5 g/dL, intraoperative blood loss of 200 mL or more, operative time of 200 minutes or more, and/or intraoperative transfusion requirement increased AL risk. Enteral nutritional optimization prior to elective surgery is essential. Proximal diversion should be considered for patients with all 3 intraoperative risk factors because they are at high risk for AL.
Preprophase microtubule bands in some abnormal mitotic cells of wheat.

Caffeine treatment of growing wheat tissues was used to form binucleate or polyploid cells; preprophase microtubules in subsequent division cycles in these and some other abnormal cells were then examined. In root tips, binucleate cells or those with greatly enlarged nuclei usually contained one transverse preprophase band of microtubules; sometimes this was slightly asymmetrical or skew, and less commonly two bands were seen. In coleoptile vascular bundles, there were generally two or more bands in the greatly elongated cells, these sometimes appearing in different planes. During formation of the stomatal complexes, preprophase microtubules were almost invariably found where expected, preceding abnormal development both in untreated and also in caffeine-treated material, regardless of the number, disposition or size of nuclei. This occurred even when wall stumps, formed during a previous abortive division, indicated that that previous division was also asymmetrical. It is concluded that the position(s) of preprophase band(s) of microtubules is not particularly influenced by the nucleus or nuclei, being more susceptible to external morphogenetic influences which can persist for some considerable time. Particularly in the case of stomatal complexes, a cell wall seems necessary to seal off or otherwise fulfil the tendency towards asymmetrical division.
Inhibitory effects of 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin on rat hepatocyte proliferation induced by 2/3 partial hepatectomy

To better understand the mode of action of 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD) induced alterations in hepatic cell proliferation and the potential link to tumour‐promoting activity, we investigated the effects of TCDD on the expression of certain key genes involved in liver cell growth and the effects of TCDD on induced hepatocyte cell proliferation. Gene expression analysis was conducted, by Northern blot hybridization, using RNA isolated from female Sprague‐Dawley rat livers collected at various times during a 14‐day dosing period with TCDD known to produce alterations in cell proliferation. No major changes were observed in the expression of the transforming growth factors TGF‐α and TGF‐β or in oncogenes ras, src and myc. However, the expression of the transcription factors C/EBP, HNF‐1 α and HNF‐4 decreased after 14 days of TCDD treatment. To investigate how TCDD affects hepatic growth, cell proliferation analysis was conducted in rats stimulated to undergo hepatocyte proliferation following either 2/3 partial hepatectomy or lead nitrate treatment. Cell proliferation was quantified by means of immunocytochemical detection of Proliferating Cell Nuclear Antigen (PCNA). Fourteen days of pretreatment with TCDD caused an overall inhibiton of hepatocytes in the growth fraction (G1, S, G2 and M) from 61 ± 3% in the control‐partial hepatectomy group to 41 ± 3% in the TCDD‐partial hepatectomy group. A periportal pattern of cell proliferation was observed in the TCDD‐partial hepatectomy group as compared to the panlobular pattern of cell proliferation in the control‐partial hepatectomy group. TCDD pretreatment also produced an inhibition of cell proliferation induced by the liver mitogen lead nitrate. TCDD‐induced inhibition of hepatocyte proliferation could play a role in TCDD tumour promotion and hepatocarcinogenesis through the creation of a environment whereby preneoplastic cells continue to expand while normal hepatocyte proliferation is inhibited.
The use of the internet in higher education: Academics' experiences of using ICTs for teaching and learning

Purpose – To explore academics’ experiences of using information and communication technologies (ICTs) for teaching and learning.Design/methodology/approach – Analysis of three discipline‐specific focus group discussions held with academics based in Higher Education Institutions (HEIs) that use ICTs for teaching their students.Findings – The most common use of ICTs in all subjects was to provide students with access to a range of online resources. Academics’ motivations for using ICTs included: enhancing the educational experience for their students; to compensate for some of the changes occurring in higher education, such as the rise in student numbers and demand for flexible learning opportunities; and personal interest and enjoyment. The difficulties academics encountered when using these technologies for teaching included: a lack of time; dissatisfaction with the software available; and copyright.Research limitations/implications – This is a small scale, exploratory study. Further research is required.
Malaria chemoprophylaxis: what do the travelers choose, and how does pretravel consultation influence their final decision.

Three different drugs (mefloquine, atovaquone/proguanil, doxycycline) are recommended for malaria chemoprophylaxis, each with approximately the same efficacy but various adverse event profiles, regimens, and prices. We investigated which medication the travelers would have chosen on the basis of written evidence-based information and the impact that pretravel consultation had on their decision. A prospective study was performed in a travel clinic and private practice, and 1073 travelers were included; 45% chose mefloquine (Lariam or Mephaquine), 21% atovaquone/proguanil (Malarone), 18% doxycycline (Supracycline), 5% "no prophylaxis," and 11% "do not know. " Lariam was principally chosen because of prior experience (38%), Mephaquine because of low price (34%), and doxycycline and Malarone because of the profile of adverse events (55% and 43%, respectively). Based on objective written information, travelers most frequently chose mefloquine for chemoprophylaxis. This suggests that evidence-based information weighs more heavily than negative publicity. Taking into account the perspective of the user should improve appropriateness of the pretravel advice.
Dominant Activity of Activation Function 1 (AF-1) and Differential Stoichiometric Requirements for AF-1 and -2 in the Estrogen Receptor α-β Heterodimeric Complex

ABSTRACT Estrogenic responses are now known to be mediated by two forms of estrogen receptors (ER), ERα and ERβ, that can function as homodimers or heterodimers. As homodimers the two have been recently shown to exhibit distinct transcriptional responses to estradiol (E2), antiestrogens, and coactivators, suggesting that the ER complexes are not functionally equivalent. However, because the three possible configurations of ER complexes all recognize the same estrogen response element, it has not been possible to evaluate the transcriptional properties of the ER heterodimer complex by transfection assays. Using ER subunits with modified DNA recognition specificity, we were able to measure the transcriptional properties of ERα-ERβ heterodimers in transfected cells without interference from the two ER homodimer complexes. We first demonstrated that the individual activation function 1 (AF-1) domains act in a dominant manner within the ERα-ERβ heterodimer: the mixed agonist-antagonist 4-hydroxytamoxifen acts as an agonist in a promoter- and cell context-dependent manner via the ERα AF-1, while activation of the complex by the mitogen-activated protein kinase (MAPK) pathway requires only the ERα- or ERβ-responsive MAPK site. Using ligand-binding and AF-2-defective mutants, we further demonstrated that while the ERα-ERβ heterodimer can be activated when only one E2-binding competent partner is present per dimer, two functional AF-2 domains are required for transcriptional activity. Taken together, the results of this study of a retinoid X receptor-independent heterodimer complex, the first such study, provide evidence of different stoichiometric requirements for AF-1 and -2 activity and demonstrate that AF-1 receptor-specific properties are maintained within the ERα-ERβ heterodimer.
Effect of compound sequence on bitterness enhancement.

The nature and occurrence of carry-over effects, i.e. the response to a stimulus is influenced by previous samples, were examined for selected bitter compounds. A time-intensity procedure was used to rate the bitterness of six compounds (caffeine, denatonium benzoate, limonin, naringin, quinine and sucrose octa-acetate). For each subject concentrations of these compounds were determined that were approximately equal in intensity to 1.18 x 10(-5) M limonin. To test carry-over effects of each compound the 36 paired sequences (pairs) were evaluated. Within a session three pairs were tested, between which two-stage rinses were used to remove any effects of the previous pairs. Within a pair only water rinses were used between stimuli. For all compounds carry-over or sensitization effects were observed in which values for maximum intensity, rate of onset and total area under the time-intensity curve were higher for a compound when tested in the second position than in the first. In addition, the degree of sensitization and susceptibility to sensitization were compound-specific. Caffeine increased the bitterness by the largest amount for all other compounds, while it was least affected. Regardless of the compound in the first position, the bitterness of quinine and denatonium were most enhanced.
Hydrophobic interaction in Candida albicans and Candida tropicalis adherence to various denture base resin materials

The effects of hydrophobicities of substrate surfaces on microbial adherence were examined by using Candida albicans and Candida tropicalis and 21 denture base resin materials. With increasing surface free energy of resin plates, increasing adherence of C. albicans and decreasing adherence of C. tropicalis were observed. The surface free energy of C. albicans is higher than that of all resin material surfaces, and C. tropicalis has surface free energy lower than that of all materials used. In calculation of the changes of free energy accompanying the adherence, the higher adherence tendency was accompanied by a lower value for the free energy change in both species. From a different standpoint, the closer the surface free energy of the substrate surface and the microorganism, the higher was the probability of adherence.
[Formation of portal venous collaterals after ligation of the portal vein for induction of liver regeneration].

PURPOSE Unilateral occlusion of the portal vein induces contralateral lobar hypertrophy - in contrast to complete portal vein occlusion which will result in a cavernous transformation. The impact of the formation of collaterals in partial portal vein occlusion is not sufficiently known. The lobar-hypertrophy- phenomenon is in clinical use for several years to induce iatrogenic liver growth to enable extended resections. After portal vein ligation in patients prior to extended hepatic resections, we noticed a perfusion of the formerly occluded side on CT. Using the well-established mini pig model, we were interested whether portal collaterals are formed as cause of the reperfusion. Ex-situ angiograms of the liver were used for the depiction of collaterals. MATERIALS AND METHODS Using a median laparotomy as access for preparation of the hepatoduodenal ligament, a proximal left portal vein ligation was performed in eight mini pigs under general anesthesia. The total arrest of the portal blood flow (except in segments VI and VII) was documented by duplex ultrasound. After 4 weeks, all pigs were sacrificed and the weight of the ligated liver segments and non-ligated liver segments was measured and compared to a sham group (n = 5). After insertion of a guiding sheath, an ex-situ DSA of the portal vein was acquired. RESULTS Compared with the sham group, the liver weight increased by 60 % (23 - 99 %, std. dev. 30 %) in segments VI and VII. Atrophy of the ligated segments was signified by a weight loss of 10 % (standard deviation 15 %). The ex-situ angiograms revealed a uniform pattern of collaterals with subsequent complete total recanalization of the formerly occluded portal vein distal from the ligation. The collaterals reduced the portal venous flow rate. CONCLUSION After portal vein ligation, uniform collateralization results in recanalization of the occluded portal vein. The extent of the collaterals exceeds the known cavernous transformation. The increase in liver volume is not restrained by the formation of collaterals.
Title Protein Microparticles for Printable Bioelectronics

In biosensors, printing involves the transfer of materials, proteins or cells to a substrate. It offers many capabilities that can be utilized in many applications, including rapid deposition and patterning of proteins or other biomolecules. However, issues such as stability when using biomaterials are very common. Using proteins, enzymes, as biomaterial ink require immobilizations and modifications due to changing in the structural conformation of the enzymes, which leads to changes in the properties of the enzyme such as enzymatic activity, during the printing procedures and requirements such as solvent solutions. In this project, an innovative approach for the fabrication of protein microparticles based on cross-linking interchange reaction is presented to increase the stability in different solvents. The idea is to decrease the contact area between the enzymes and the surrounding environment and also prevent conformation changes by using protein microparticles as an immobilization technique for the enzymes. The theory is based on using a cross-linking reagent trigging the formation of intermolecular bonds between adjacent protein molecules leading to assembly of protein molecules within a CaCO3 template into a microparticle structure. The CaCO3 template is removed by changing the solution pH to 5.0, leaving behind pure highly homogenous protein microparticles with a size of 2.4 ± 0.2 μm, according to SEM images, regardless of the incubation solvents. The enzyme model used is Horse Radish Peroxidase (HRP) with Bovine Serum Albumin (BSA) and Glutaraldehyde (GL) as a cross-linking reagent. Furthermore, a comparison between the enzymatic activity of the free HRP and the BSA-HRP protein microparticles in buffer and different solvents are obtained using Michaelis-Menten Kinetics by measuring the absorption of the blue product produced by the enzyme-substrate interaction using a multichannel spectrophotometer with a wavelength of 355 nm. 3,3’,5,5’tetramethylbenzidine (TMB) was used as substrate. As a result, the free HRP show an enzymatic activity variation up to ± 50 % after the incubation in the different solvents while the protein microparticles show much less variation which indicate a stability improvement. Moreover, printing the microparticles require high microparticle concentration due to contact area decreasing. However, using microparticles as a bioink material prevent leakage/diffusion problem that occurs when using free protein instead.