Miracle-dz/UniFAR-FTUs huggingface dataset:
Ductal cells of minor salivary glands in Sjögren's syndrome express LINE‐1 ORF2p and APOBEC3B

BACKGROUND Type I interferon activation is a hallmark event in Sjögren's syndrome. L1 retroelements stimulate plasmacytoid dendritic cells, activating the type I interferons, and are regulated by various mechanisms, including the APOBEC3 deaminases. As L1s are potential trigger factors in autoimmunity, we aimed to investigate the immunohistochemical localization of L1 ORF2p and its inhibitor APOBEC3B protein in minor salivary glands of Sjögren's syndrome patients. METHODS Twenty minor salivary gland-tissue samples from 20 Sjögren's syndrome patients, classified according to Tarpley's histological criteria, and 10 controls were evaluated for L1 ORF2p and APOBEC3B expression via immunohistochemistry. RESULTS L1 ORF2p was expressed in 17/20 SS patients and all controls. APOBEC3B expression was observed in 15/20 Sjögren's syndrome patients, 5/5 chronic sialadenitis, and 3/5 normal minor salivary glands. Both antibodies stained the cytoplasm of the ductal epithelial cells. Negative staining was observed in the acinar cells. L1 ORF2p-positive immunostaining was significantly lower in Tarpley IV Sjögren's syndrome patients than controls (P = .039), and APOBEC3B-positive staining was significantly lower in Tarpley I compared to Tarpley II Sjögren's syndrome patients (P = .008) and controls (P = .035). CONCLUSIONS L1 ORF2p and APOBEC3B are expressed in the ductal epithelial cells of minor salivary glands that are among the key targets in Sjögren's syndrome. L1 ORF2p expression may promote the L1 ability to act as an intrinsic antigen in Sjögren's syndrome. The potential future use of L1 ORF2-reverse transcriptase inhibitors in autoimmunity supports further investigation of L1 epigenetic regulation by APOBEC3 enzymes.
Increased Adiposity at Diagnosis in Younger Children With Type 1 Diabetes Does Not Persist

In contrast to the results of our study (1), d’Annunzio et al. (2) did not find younger children to be more obese at diagnosis compared with older children and speculate that our purported threshold of higher adiposity for earlier onset of type 1 diabetes has not been reached in Italy yet. We agree with their speculation; younger Italian children had a much lower BMI SD score (SDS) (0.26) …
Influence of age and inoculum level on shed pattern of Salmonella typhimurium in chickens.

SUMMARY Groups of chickens aged 2 days and 1, 2, 4, and 8 weeks were inoculated orally with either 102, 104, 106, 108, or 1010 viable cells of a strain of Salmonella typhimurium. They were maintained in wirefloored cages in isolated quarters, and cloacal swabs were taken from each bird and cultured for salmonellae at selected intervals from the 3rd to 94th day. Level of intestinal infection as evidenced by fecal shedding of viable salmonellae was correlated with bird age and inoculum dose. Stressing nonshedding birds did not influence the shedding pattern significantly. Only 8% of all inoculated birds were still shedding on the 38th day, only 1% on the 73rd, and 0.5% on the 94th. Necropsies with bacteriological culturing between the 77th and 115th days revealed intestinal infection in 1 bird that had shed continuously and in 6 that had stopped shedding 22 to 79 days previously. Mortality was 25 to 50% in the 2-day-old birds, but no deaths attributable to salmonella infection occurred in the older groups. Repetition of portions of the experiment with a recently isolated field strain of Salmonella typhimurium gave comparable results.
Zinc co‐localizes with GABA and glycine in synapses in the lamprey spinal cord

The presence of zinc in synaptic terminals in the lamprey spinal cord was examined utilizing a modification of the Timm′s sulfide silver method and with the fluorescent marker 6‐methoxy‐8‐quinolyl‐p‐toluenesulfonamide (TSQ). Axons labeled with a Timm′s staining method were predominantly located in the lateral region of the dorsal column. This correlated with a maximum of TSQ fluorescence in this region of the spinal cord. Single labeled terminals accumulating Timm reaction product were also found throughout the gray matter and fiber tracts. At the ultrastructural level, zinc was located in a population of synaptic terminals that co‐localized γ‐aminobutyric acid (GABA) and glycine. Possible effects of Zn2+ on neuronal activity were examined. In spinobulbar interneurons, which receive GABAergic input in the dorsal column, zinc potentiated responses to GABA application, but it did not affect responses to GABA in motoneurons. Responses in motoneurons to pressure application of glycine were also not affected by Zn2+. Zinc, however, potentiated monosynaptic glycinergic inhibitory postsynaptic potentials (IPSPs) evoked in motoneurons by inhibitory locomotor network interneurons and increased frequency, but not amplitude of spontaneous miniature IPSPs recorded in the presence of tetrodotoxin (TTX), suggesting presynaptic effects. Glutamate responses and the amplitude of monosynaptic excitatory postsynaptic potentials (EPSPs) in motoneurons were reduced by zinc. These effects appeared to be mediated largely postsynaptically through an effect on the N‐methyl‐D‐aspartate (NMDA) component of the glutamatergic input. Our results thus show that free zinc is present in inhibitory synaptic terminals in the lamprey spinal cord, and that it may function as a modulator of inhibitory synaptic transmission. J. Comp. Neurol. 433:208–221, 2001. © 2001 Wiley‐Liss, Inc.
Biomechanical Evaluation of the Extensor Musculature of the Cervical Spine

Dissection of the musculature in the cervical spines of four cadavers indicated that the semispinalis cervicis and capitis muscles appeared to be the muscles primarily responsible for extension of the cervical spine and head. The minimum force needed to balance a biomechanical model of the cervical spine in the neutral prone position against gravity measured 14.38 kg. The values obtained with this model, with roentgenograms of the cervical spine, and vector analysis were close enough to establish that the model is apparently valid for studying the extensor musculature of the cervical spine. Because the extensors appear to generate considerable force and may act as significant dynamic stabilizers of the cervical spine, the authors have altered their posterior surgical approach to minimize disruption of the extensor musculature.
Onset of white striping and progression into wooden breast as defined by myopathic changes underlying Pectoralis major growth. Estimation of growth parameters as predictors for stage of myopathy progression

ABSTRACT The broiler industry has incurred significant economic losses due to two muscle myopathies, white striping (WS) and wooden breast (WB), affecting the Pectoralis major (P. major) of commercial broilers. The present study documented macroscopic changes occurring with age/growth in the P. major and P. minor muscles of commercial broilers from day 2 through day 46 (n = 27/day). Distinct myopathic aberrations observed in both breast muscles corresponded to the onset of WB. These distinct morphological changes were used as determinants in developing a ranking system, defining the ontogeny of WB as the following four stages: (1) WS, (2) petechial epimysium haemorrhages, (3) intramuscular haemorrhages and (4) ischaemia. A cumulative logit proportional odds model was used to relate the rank probabilities with the following growth parameters: body weight, P. major and P. minor weight/yield/length/width/depth. The best-fit model included P. major length/width/depth, P. minor width, P. major and P. minor yield as predictors for rank. Increasing P. major depth, P. minor width and P. major yield increased the odds of falling into higher ranks (more severe myopathy). Conversely, increasing P. major length, P. major width and P. minor yield increased the odds of falling into smaller ranks (less severe myopathy). This study describes the macroscopic changes associated with WB ontogeny in the development of a ranking system and the contribution of growth parameters in the determination of rank (WB severity). Results suggest that physical measurements inherent to selection for high-yielding broiler genotypes are contributing to the occurrence and severity of WS and WB.
Tensile Strength and Collagen Content of Amniotic Membrane Do Not Change After the Second Trimester Or During Delivery

We studied the tensile strength and collagen content of the amniotic membrane in the early and late second trimester and at term in specimens obtained after spontaneous, cesarean, and prostaglandin- and stretch-induced deliveries. No significant difference in either tensile strength or collagen content was found among any group of samples. Collagenous tissue of the amnion seems to differ constitutionally from that of the cervix and vagina and to be modulated by different mechanisms during pregnancy and delivery. It also seems to resist strong physiologic tension until it is mechanically ruptured during delivery
Laminin alpha2 muscular dystrophy: genotype/phenotype studies of 22 patients.

OBJECTIVE To determine the number of primary laminin alpha2 gene mutations and to conduct genotype/phenotype correlation in a cohort of laminin alpha2-deficient congenital muscular dystrophy patients. BACKGROUND Congenital muscular dystrophies (CMD) are a heterogeneous group of muscle disorders characterized by early onset muscular dystrophy and a variable involvement of the CNS. Laminin alpha2 deficiency has been reported in about 40 to 50% of cases of the occidental, classic type of CMD. Laminin alpha2 is a muscle specific isoform of laminin localized to the basal lamina of muscle fibers, where it is thought to interact with myofiber membrane receptor, such as integrins, and possibly dystrophin-associated glycoproteins. METHODS Seventy-five CMD patients were tested for laminin alpha2 expression by immunofluorescence and immunoblot. The entire 10 kb laminin alpha2 coding sequence of 22 completely laminin alpha2-deficient patients was screened for causative mutations by reverse transcription (RT)-PCR/single strand conformational polymorphisms (SSCP) analysis and protein truncation test (PTT) analysis followed by automatic sequencing of patient cDNA. Clinical data from the laminin alpha2-deficient patients were collected. RESULTS Thirty laminin alpha2-negative patients were identified (40% of CMD patients tested) and 22 of them were screened for laminin alpha2 mutations. Clinical features of laminin alpha2-deficient patients were similar, with severe floppiness at birth, delay in achievement of motor milestones, and MRI findings of white matter changes with normal intelligence. Loss-of-function mutations were identified in 95% (21/22) of the patients studied. SSCP analysis detected laminin alpha2 gene mutations in about 50% of the mutant chromosomes; PTT successfully identified 75% of the mutations. A two base pair deletion mutation at position 2,096-2,097 bp was present in 23% of the patients analyzed. CONCLUSIONS Our data suggest that the large majority of laminin alpha2-deficient patients show laminin alpha2 gene mutations.
Regional brain variations of cytochrome oxidase activity in Relnrl‐orl mutant mice

Cell malpositioning has been described in laminated structures of the spontaneous mutation, reeler, including the cerebellum, the hippocampus, and the neocortex. Despite the ectopic positions of different neuronal populations, the specificity of synaptic connections is maintained. The metabolic consequences of this form of neuropathology were examined in Relnrl mutant mice by quantitative measures of cytochrome oxidase (CO) activity, a mitochondrial enzyme essential for oxidative metabolism in neurons. Despite severe tissue disorganization but in line with the intact synaptic organization, the reeler mutation did not affect global metabolic activity of the laminated structures of the brain. CO activity, however, was altered in specific subregions of the cerebellum, hippocampus, and neocortex, as well as in septum and various brainstem (medial pontine, paramedial reticular, paragigantocellular reticular) regions anatomically related to these structures, attesting to large functional alterations in Relnrl‐orl brain. Metabolic activity variations were also detected in the ventral tegmental area and ventral neostriatum of the mesolimbic dopaminergic pathway. The results are discussed and compared to the regional CO variations found in other ataxic mice, in regard to the structural defects, the integrity of the connections, and the mutation‐specific effects. © 2006 Wiley‐Liss, Inc.
Role of follicle stimulating hormone and epidermal growth factor in the development of porcine preantral follicle in vitro

Summary The aim of the present study was to assess the role of follicle stimulating hormone (FSH), epidermal growth factor (EGF) or a combination of EGF and FSH on the in vitro growth of porcine preantral follicles, estradiol secretion, antrum formation, oocyte maturation and subsequent embryonic development. Porcine preantral follicles were cultured for 3 days in the absence or in the presence of FSH or EGF. Oocytes from these follicles were then matured, fertilized in vitro and embryos were cultured. Estradiol secretion and histological analysis of cultured follicles were also carried out. The results showed that when FSH, or a combination of EGF and FSH, was added to the culture medium, most of preantral follicles grew to antral follicles with high estradiol secretion and the oocytes from these antral follicles could mature, fertilize and develop to the blastocyst stage. Without FSH, or a combination of EGF and FSH, preantral follicles were unable to develop to the antral stage. Histology demonstrated that the resulting follicles were nonantral, estradiol production was reduced and none of their oocytes matured after in vitro maturation. The results indicate the essential role of FSH in promoting in vitro growth of porcine preantral follicle, estradiol secretion, antrum formation, oocyte maturation and subsequent embryonic development. EGF with FSH treatment of porcine preantral follicles improves the quality of oocytes, shown by a higher frequency of embryonic development.
Closed-Chamber Inhalation Pharmacokinetic Studies with Hexamethyldisiloxane in the Rat

Gas uptake methods together with physiologically based pharmacokinetic (PBPK) modeling have been used to assess metabolic parameters and oral absorption rates for a wide variety of volatile organic compounds. We applied these techniques to study the in vivo metabolism of hexamethyldisiloxane (HMDS), a volatile siloxane with low blood/air (partition coefficient PB ≈ 1.00) and high fat/blood partitioning (partition coefficient PF ≈ 300). In contrast to other classes of metabolized volatiles, metabolic parameters could only be estimated from closed-chamber results with confidence by evaluating both closed-chamber disappearance curves and constant concentration inhalation studies. The constant-concentration inhalation results refine the estimate of the blood/air partition coefficient and constrain model structure for storage of the lipophilic compound in blood and tissues. The gas uptake results, from Fischer 344 rats (male, 8-9 wk old) exposed to initial HMDS air concentrations from 500 to 5000 ppm, were modeled with a 5-tissue PBPK model. Excellent fits were obtained with diffusion-limited uptake of HMDS in fat and a lipid storage pool in the blood. Metabolism, restricted to the liver, was described as a single saturable process (V max = 113.6 µmol/h/kg; K m = 42.6 µmol/L) and was affected by inhibitors (diethyldithiocarbamate) or inducers (phenobarbital) of cytochrome P-450s. Exhalation kinetics of HMDS after oral/intraperitoneal administration showed low bioavailability and significant lag times, also quite different from results of other classes of volatile hydrocarbons. In general, estimates of metabolic clearance by gas uptake studies were improved by simultaneous examination of time-course results from constant concentration inhalation studies. This conclusion is likely to hold for any volatile lipophilic compound with low blood/air partitioning.
170° Wide-Angle Colonoscope: Effect on Efficiency and Miss Rates

BACKGROUND:Small polyps are routinely missed during colonoscopy even with careful examination.AIM:To determine and compare endoscopic efficiency and polyp miss rate between a prototype 170° wide-angle (WA) colonoscope and a standard (S) colonoscope.METHODS:Two consecutive same-day colonoscopies were performed in 50 patients with intact colons. The patients were randomized to undergo the first colonoscopy with either the prototype WA 170° angle of view colonoscope or an S adult 140° angle of view colonoscope.RESULTSThe mean time for insertion was 2.09 (1.09) min versus 2.53 (1.47) min (p = 0.002) for the WA colonoscope and the S colonoscope, respectively. Similarly, the mean time for examination during withdrawal was shorter with the WA colonoscope (4.98 (0.94) vs 5.74 (1.12) min; p < 0.0001). The mean insertion time for the second examination was shorter than the insertion time for the first examination, irrespective of the colonoscope (p = 0.006). However, the withdrawal times were not significantly different between the first and second examinations (p = 0.11). The miss rate for all polyps with the WA colonoscope (19%) was similar to the miss rate with the S colonoscope (27%; p = 0.19). The miss rates for adenomas with the WA (10/33; 30.3%) and the S scope (15/50; 30%) were similar (p = 0.98). CONCLUSIONS:The use of the WA colonoscope was associated with a reduction in insertion time to the cecum, as well as examination time during withdrawal. No evidence was found that the accuracy of the two colonoscopes differs.
Long-term influence of feeding barley treated with lactic acid and heat on performance and energy balance in dairy cows

ABSTRACT The study evaluated the long-term influence of feeding ground barley treated with lactic acid (LA) alone or with LA and heat on performance, energy and protein balance in dairy cows. Thirty cows were fed three diets differing in the treatment of barley grain, either unprocessed ground barley (Control), ground barley steeped in 1% LA at room temperature (LA-treated barley) or ground barley steeped in 1% LA with an additional heating at 55°C (LAH-treated barley). Cows were studied from week 3 to 17 post-partum. Dry matter intake (DMI), milk yield and composition and body weight (BW) were measured daily. Estimated energy and protein balances were calculated and blood samples were collected three times during the experiment and analysed for common metabolites of energy and lipid metabolism. Digestibility of different treated barley and other dietary ingredients was investigated in vivo using four wethers. The treatment of barley with LA and LAH increased the digestibility of organic matter (OM) by approximately 5% and the content of metabolisable energy by 0.5–0.6 MJ/kg DM. Data showed no effect of feeding diets containing LA- or LAH-treated barley at 39% of DM on overall DMI, BW, BW change, milk production and composition and on the blood variables studied. Diet influenced the estimated balances of net energy of lactation (p < 0.01) and the content of utilisable protein at the duodenum (p = 0.07) with cows fed the diet with LA-treated barley showing improved balances. In conclusion, feeding diets containing LA- or LAH-treated barley had no influence on performance, milk composition and blood metabolites, but LA treatment without heat seems to improve the energy balance of cows.
Alda-1 Attenuates Lung Ischemia-Reperfusion Injury by Reducing 4-Hydroxy-2-Nonenal in Alveolar Epithelial Cells

Objectives: Excessive oxidative stress is a main cause of lung ischemia-reperfusion injury, which often results in respiratory insufficiency after open-heart surgery for a cardiopulmonary bypass. Previous studies demonstrate that the activation of aldehyde dehydrogenase-2 could significantly reduce the oxidative stress mediated by toxic aldehydes and attenuate cardiac and cerebral ischemia-reperfusion injury. However, both the involvement of aldehydes and the protective effect of the aldehyde dehydrogenase-2 agonist, Alda-1, in lung ischemia-reperfusion injury remain unknown. Design: Prospective laboratory and animal investigation were conducted. Setting: State Key Laboratory of Cardiovascular Disease. Subjects: Primary human pulmonary alveolar epithelial cells, human pulmonary microvascular endothelial cells, and Sprague-Dawley rats. Interventions: A hypoxia/reoxygenation cell-culture model of human pulmonary alveolar epithelial cell, human pulmonary microvascular endothelial cell, and an isolated-perfused lung model were applied to mimic lung ischemia-reperfusion injury. We evaluated the effects of Alda-1 on aldehyde dehydrogenase-2 quantity and activity, on aldehyde levels and pulmonary protection. Measurements and Main Results: We have demonstrated that ischemia-reperfusion–induced pulmonary injury concomitantly induced aldehydes accumulation in human pulmonary alveolar epithelial cells and lung tissues, but not in human pulmonary microvascular endothelial cells. Moreover, Alda-1 pretreatment significantly elevated aldehyde dehydrogenase-2 activity, increased surfactant-associated protein C, and attenuated elevation of 4-hydroxy-2-nonenal, apoptosis, intercellular adhesion molecule-1, inflammatory response, and the permeability of pulmonary alveolar capillary barrier, thus alleviated injury. Conclusions: Our study indicates that the accumulation of 4-hydroxy-2-nonenal plays an important role in lung ischemia-reperfusion injury. Alda-1 pretreatment can attenuate lung ischemia-reperfusion injury, possibly through the activation of aldehyde dehydrogenase-2, which in turn removes 4-hydroxy-2-nonenal in human pulmonary alveolar epithelial cells. Alda-1 pretreatment has clinical implications to protect lungs during cardiopulmonary bypass.
Bayesian Portfolio Analysis

This paper reviews the literature on Bayesian portfolio analysis. Information about events, macro conditions, asset pricing theories, and security-driving forces can serve as useful priors in selecting optimal portfolios. Moreover, parameter uncertainty and model uncertainty are practical problems encountered by all investors. The Bayesian framework neatly accounts for these uncertainties, whereas standard statistical models often ignore them. We review Bayesian portfolio studies when asset returns are assumed both independently and identically distributed as well as predictable through time. We cover a range of applications, from investing in single assets and equity portfolios to mutual and hedge funds. We also outline challenges for future work.
Trigger factor is involved in GroEL‐dependent protein degradation in Escherichia coli and promotes binding of GroEL to unfolded proteins.

In Escherichia coli, the molecular chaperones of hsp60/hsp10 (GroEL/GroES) families are required not only for protein folding but also for the rapid degradation of certain abnormal proteins. The rate‐limiting step in the degradation of the fusion protein CRAG by protease ClpP appears to be the formation of a complex with GroEL. We have isolated these complexes and found that each GroEL 14mer contained a short‐lived fragment of CRAG plus a 50 kDa polypeptide, which we identified by sequencing and immunological methods as Trigger Factor (TF). Upon ATP addition, GroEL and TF dissociated together from CRAG but remained tightly associated with each other even upon gel filtration. TF was originally proposed to function in protein translocation across membranes but altering cellular content of TF did not affect this process in vivo. By contrast, low levels of TF expression markedly reduced CRAG degradation, while an overproduction of TF greatly stimulated this process. Furthermore, in extracts of cells expressing high levels of TF, the capacity of GroEL to bind to CRAG is greatly increased. Overproduction of TF also stimulated GroEL's ability to bind to other unfolded proteins (fetuin and histone). Thus, TF is a rate‐limiting factor for CRAG degradation; it appears to regulate GroEL function and to promote the formation of TF‐GroEL‐CRAG complexes which are critical for proteolysis.