julilili42/papers huggingface dataset:
Chylomicron components activate duodenal vagal afferents via a cholecystokinin A receptor‐mediated pathway to inhibit gastric motor function in the rat
2003-05-27

Nutrients in the intestine initiate changes in secretory and motor function of the gastrointestinal (GI) tract. The nature of the ‘sensors’ in the intestinal wall is not well characterized. Intestinal lipid stimulates the release of cholecystokinin (CCK) from mucosal entero‐endocrine cells, and it is proposed that CCK activates CCK A receptors on vagal afferent nerve terminals. There is evidence that chylomicron components are involved in this lipid transduction pathway. The aim of the present study was to determine (1) the pathway mediating reflex inhibition of gastric motility and (2) activation of duodenal vagal afferents in response to chylomicrons. Mesenteric lymph was obtained from awake rats fitted with lymph fistulas during intestinal perfusion of lipid (Intralipid, 170 μmol h −1 , chylous lymph) or a dextrose and/or electrolyte solution (control lymph). Inhibition of gastric motility was measured manometrically in urethane‐anaesthetized recipient rats in response to intra‐arterial injection of lymph close to the upper GI tract. Chylous lymph was significantly more potent than control lymph in inhibiting gastric motility. Functional vagal deafferentation by perineural capsaicin or CCK A receptor antagonist (devazepide, 1 mg kg −1 , I.V.) significantly reduced chylous lymph‐induced inhibition of gastric motility. The discharge of duodenal vagal afferent fibres was recorded from the dorsal abdominal vagus nerve in an in vitro preparation of the duodenum. Duodenal vagal afferent nerve fibre discharge was significantly increased by close‐arterial injection of CCK (1‐100 pmol) in 43 of 83 units tested. The discharge of 88 % of CCK‐responsive fibres was increased by close‐arterial injection of chylous lymph; devazepide (100 μg, I.A.) abolished the afferent response to chylous lymph in 83 % of these units. These data suggest that in the intestinal mucosa, chylomicrons or their products release endogenous CCK which activates CCK A receptors on vagal afferent nerve fibre terminals, which in turn initiate a vago‐vagal reflex inhibition of gastric motor function.
Th2 cells shape the differentiation of developing T cell responses during interactions with dendritic cells in vivo
2003-05-27

Abstract During priming, naive CD4 + Th cells differentiate into cells that produce either IFN‐γ or IL‐4. Even though the cascade of pathways that induces IL‐4‐producing Th2 cells has been determined in vitro , the signals promoting Th2 differentiation under physiological conditions remain enigmatic, especially the natural role of the single most important Th2‐inducing signal,IL‐4. Using Th2 and naive Th cells, each expressing a distinct transgenic TCR, here we show that Th2 cells migrate with the same dynamics as naive Th cells in draining lymph nodes and bind to the same DC, when driven by antigen in complete Freund's adjuvant (CFA). Th2‐cell‐derived IL‐4 deviates CFA‐induced Th1 development toward a Th2 phenotype, if both cell populations co‐localize in the same T cell area, and are activated simultaneously. Thus, intranodal Th2 cells directly influence Th cell differentiation in vivo , but only under restricted conditions. These findings have implications for the design of cytokine‐based therapies and explain the spreading of Th2 responses to multiple aeroallergens in allergic asthma, where naive Th and Th2 cells co‐localize in lung‐draining lymph nodes.
Sodium-Inorganic Phosphate Cotransporter NaPi-IIb in the Epididymis and Its Potential Role in Male Fertility Studied in a Transgenic Mouse Model
2003-05-28

Analysis by cDNA microarrays showed that in the murine epididymis, NaPi-IIb was the predominantly expressed epithelial isoform of the sodium-inorganic phosphate cotransporter and was markedly overexpressed in the proximal region in the infertile knockout (KO) compared to the fertile heterozygous (HET) c-ros transgenic mouse. The apparent up-regulation in the KO mouse confirmed by Northern and Western blot analyses could be explained by the absence of NaPi-IIb from the initial segment of the HET epididymis, as revealed by immunohistochemistry, and its presence on the epithelial brush border throughout the proximal epididymis of KO mice, where differentiation of the initial segment fails to occur. Both NaPi-IIb mRNA and protein were scarce or absent from the cauda epididymidis of both genotypes. A high content of inorganic phosphate was measured enzymatically in the HET cauda luminal fluid, with a 27% decrease in the KO mice. This decrease, presumably from a greater reabsorption of inorganic phosphate, particularly in the initial part of the KO epididymis, may disturb the normal process of sperm maturation in these infertile males. By contrast, no apparent consequences were observed for the transport of Na+ and Ca2+, the concentrations of which (approximately 26 mM and approximately 30 microM, respectively) were measured by microelectrodes to be identical in the caudal fluid from both genotypes.
Two-Electron-Transfer Redox Systems, Part 7: Two-Step Electrochemical Oxidation of the Boron Subhalide Cluster Dianions (X = Cl, Br, I)
2003-05-28

Boron subhalide cluster dianions B6X 2- 6 (X = Cl, Br, I) are electrochemically oxidized in two steps. According to cyclic voltammograms, the first step is chemically reversible and yields the corresponding radical anions B6X .- 6. The electron transfer is nearly diffusion controlled. The second, slower electron-transfer step leads to a species which we assume to be the hitherto not yet described neutral compounds B6X 2- 6. The voltammograms indicate a coupled fast catalytic reaction, producing the radical anions in a reduction by an electrolyte component. Computer simulations of the cyclic voltammograms reveal mechanistic details of the redox reactions, as well as quantitative values for formal potentials, rate constants, and diffusion coefficients. The results are compared to other BnXn redox systems.
Comments on chapters 1 and 2
2003-05-29

Reflecting upon the nature of the Roman Empire in the fifth decade before Christ, Cicero stated what was to be a key point in the classical heritage. There was but one right law – just as there was one right reason. “[A]ll nations at all times will be bound by this eternal and unchangeable law.” The political implication was clear: reason being law, all people sharing reason, they also share the law – “and those who have these things in common must be considered members of the same state.” This membership was what differentiated human beings from animals and made them resemble gods. The way to Empire, too, was firmly set: “Do we not see that the best people are given the right to rule by nature herself, with the greatest benefit to the weak?” Rome is law, law is reason, reason is universal: Rome is universal.
Gene therapy: prospects for glycolipid storage diseases
2003-05-29

Lysosomal storage diseases comprise a group of about 40 disorders, which in most cases are due to the deficiency of a lysosomal enzyme. Since lysosomal enzymes are involved in the degradation of various compounds, the diseases can be further subdivided according to which pathway is affected. Thus, enzyme deficiencies in the degradation pathway of glycosaminoglycans cause mucopolysaccharidosis, and deficiencies affecting glycopeptides cause glycoproteinosis. In glycolipid storage diseases enzymes are deficient that are involved in the degradation of sphingolipids. Mouse models are available for most of these diseases, and some of these mouse models have been used to study the applicability of in vivo gene therapy. We review the rationale for gene therapy in lysosomal disorders and present data, in particular, about trials in an animal model of metachromatic leukodystrophy. The data of these trials are compared with those obtained with animal models of other lysosomal diseases.
Inductively coupled rf coils for examinations of small animals and objects in standard whole‐body MR scanners
2003-05-30

Inductively coupled solenoid coils fitting to objects in the size of mice or rats were developed to adapt modern whole‐body MR scanners featuring sufficient gradient strength for animal examinations with high spatial resolution. Homogenous receiver characteristics is achievable over almost the whole inner region of the solenoid coils. The SNR can be increased by a factor 2 to 6 with the adapting coils for examinations using the head coil as connected receiver. Standard sequences on clinical 1.5 T scanners can be applied with adapted transmitter voltages. For example, a SNR value of about 30 is achievable in a mouse liver after 10 minutes measuring time using a 2‐D spin echo imaging sequence and a size of for the picture elements.
Toxicity of platinum compounds
2003-06-01

Since the introduction of platinum-based combination chemotherapy, particularly cisplatin, the outcome of the treatment of many solid tumours has changed. The leading platinum compounds in cancer chemotherapy are cisplatin, carboplatin and oxaliplatin. They share some structural similarities; however, there are marked differences between them in therapeutic use, pharmacokinetics and adverse effects profiles [1-4]. Compared to cisplatin, carboplatin has inferior efficacy in germ-cell tumour, head and neck cancer and bladder and oesophageal carcinoma, whereas both drugs seem to have comparable efficacy in advanced non-small cell and small cell lung cancer as well as ovarian cancer [5-7]. Oxaliplatin belongs to the group of diaminocyclohexane platinum compounds. It is the first platinum-based drug that has marked efficacy in colorectal cancer when given in combination with 5-fluorouracil and folinic acid [8,9]. Other platinum compounds such as oral JM216, ZD0473, BBR3464 and SPI-77, which is a pegylated liposomal formulation of cisplatin, are still under investigation [10-13], whereas nedaplatin has been approved in Japan for the treatment of non-small cell lung cancer and other solid tumours. This review focuses on cisplatin, carboplatin and oxaliplatin.
Conjugative Plasmid Transfer in Gram-Positive Bacteria
2003-06-01

SUMMARY Conjugative transfer of bacterial plasmids is the most efficient way of horizontal gene spread, and it is therefore considered one of the major reasons for the increase in the number of bacteria exhibiting multiple-antibiotic resistance. Thus, conjugation and spread of antibiotic resistance represents a severe problem in antibiotic treatment, especially of immunosuppressed patients and in intensive care units. While conjugation in gram-negative bacteria has been studied in great detail over the last decades, the transfer mechanisms of antibiotic resistance plasmids in gram-positive bacteria remained obscure. In the last few years, the entire nucleotide sequences of several large conjugative plasmids from gram-positive bacteria have been determined. Sequence analyses and data bank comparisons of their putative transfer ( tra ) regions have revealed significant similarities to tra regions of plasmids from gram-negative bacteria with regard to the respective DNA relaxases and their targets, the origins of transfer ( oriT ), and putative nucleoside triphosphatases NTP-ases with homologies to type IV secretion systems. In contrast, a single gene encoding a septal DNA translocator protein is involved in plasmid transfer between micelle-forming streptomycetes. Based on these clues, we propose the existence of two fundamentally different plasmid-mediated conjugative mechanisms in gram-positive microorganisms, namely, the mechanism taking place in unicellular gram-positive bacteria, which is functionally similar to that in gram-negative bacteria, and a second type that occurs in multicellular gram-positive bacteria, which seems to be characterized by double-stranded DNA transfer.
Present state and future prospects for groundwater ecosystems
2003-06-01

Ecological and socioeconomic aspects of subterranean hydrosystems have changed during the past 40–50 years. The major environmental pressures (mainly anthropogenic ones) impact the quantity and quality of groundwater resources and the state of subsurface ecosystems, and it is expected that the environmental pressures on groundwater will continue, at least until 2025, unless new environmental policies change this state of affairs. The world demographic increase and the general rise of water demand constitute one of the major environmental pressures on groundwater ecosystems especially in less developed countries in Africa, Asia and South America. Specific human activities leading to the depletion of groundwater reserves include agricultural practices, landscape alteration, urbanization demand for domestic and public drinking water, various industrial activities such as thermoelectric production and mining, and the rise of tourism in coastal areas. Climate change is contributing to the water crisis too, especially in areas with arid climate and/or in some humid monsoonal countries. The overload of aquifers with pollutants derived from agriculture (fertilizers and pesticides), from industry (release of hydrocarbon chemicals, especially spills), from waste and industrial waters, from domestic and industrial landfills, from the infiltration of pollutants from surface and from the intrusion of saline water affect groundwater quality. The dangerous increase in contaminated subsurface sites with chemicals and microbial pathogens brings with it health risks to humans. Changes of redox condition in groundwater zones, changes of biological diversity, vegetation changes with modification of agriculture practices and impacts at the biosphere scale, such as the increase in the concentration of nitrous oxides in the atmosphere, all impact groundwater ecosystems. Groundwater ecosystems must be better investigated and understood. Economic, social and ecological lines of thinking have to be combined in order to achieve meaningful policies for the sustainable development of groundwater reserves and for the protection of subsurface ecosystems. Practical measures and ideas for the development of policies up to the 2025 time-horizon should improve the sustainable usage of the world's groundwater resources.
RNA Polymerase I Transcribes Procyclin Genes and Variant Surface Glycoprotein Gene Expression Sites in Trypanosoma brucei
2003-06-01

ABSTRACT In eukaryotes, RNA polymerase (pol) I exclusively transcribes the large rRNA gene unit (rDNA) and mRNA is synthesized by RNA pol II. The African trypanosome, Trypanosoma brucei , represents an exception to this rule. In this organism, transcription of genes encoding the variant surface glycoprotein (VSG) and the procyclins is resistant to α-amanitin, indicating that it is mediated by RNA pol I, while other protein-coding genes are transcribed by RNA pol II. To obtain firm proof for this concept, we generated a T. brucei cell line which exclusively expresses protein C epitope-tagged RNA pol I. Using an anti-protein C immunoaffinity matrix, we specifically depleted RNA pol I from transcriptionally active cell extracts. The depletion of RNA pol I impaired in vitro transcription initiated at the rDNA promoter, the GPEET procyclin gene promoter, and a VSG gene expression site promoter but did not affect transcription from the spliced leader (SL) RNA gene promoter. Fittingly, induction of RNA interference against the RNA pol I largest subunit in insect-form trypanosomes significantly reduced the relative transcriptional efficiency of rDNA, procyclin genes, and VSG expression sites in vivo whereas that of SL RNA, αβ-tubulin, and heat shock protein 70 genes was not affected. Our studies unequivocally show that T. brucei harbors a multifunctional RNA pol I which, in addition to transcribing rDNA, transcribes procyclin genes and VSG gene expression sites.
Chapter 12: Human Papillomavirus Technologies
2003-06-01

Currently, human papillomavirus (HPV) DNA tests validated in large trials and epidemiological studies are the hybrid capture second-generation (HC2) HPV DNA assay and a variety of polymerase chain reaction (PCR) protocols employing degenerate or consensus primers. This article describes the currently available technology for HPV detection and discusses novel technologies and their potential for large-scale screening. Ideally, an HPV test should allow detection of multiple HPV types, identify individual types, and provide quantitative information about the viral load of each individual type found. Moreover, it should be easy to perform, be highly reproducible, with a high specificity and sensitivity, and amenable for high throughput analysis and automation. Because we do not yet fully understand the true value of viral load and the biological relevance of the different HPV types, any HPV test should be able to detect the clinically relevant high-risk types with a sufficient sensitivity of at least 10 000 genome copies per sample. To validate the different current and future test systems and to compare inter-laboratory performance we urgently need reference samples, validated reagents, and standardized protocols.
The thought-translation device (TTD): neurobehavioral mechanisms and clinical outcome
2003-06-01

The thought-translation device (TTD) consists of a training device and spelling program for the completely paralyzed using slow-cortical brain potentials (SCP). During the training phase, the self-regulation of SCPs is learned through visual-auditory feedback and positive reinforcement of SCPs; during the spelling phase, patients select letters or words with their SCPs. A psychophysiological system for detection of cognitive functioning in completely paralyzed patients is an integral part of the TTD. The neurophysiological and anatomical basis of SCP-regulation was investigated by recording of BOLD-response in functional magnetic resonance imaging. Results showed involvement of basal ganglia and premotor cortex for required SCP positivity. The clinical outcome of 11 paralyzed patients using the TTD and quality of life of severely paralyzed patients is described. First attempts to improve learning of brain regulation with transcranial magnetic stimulation were successful.
On the Form and Interpretation of German Wh-Infinitives
2003-06-01

This paper is about a minor and so far neglected sentence type in German: wh-root infinitivals such as Wohin gehen? ‘Where (should one/we) go?’. I concentrate on describing their formal and interpretive properties in detail, and relate these properties in a nonarbitrary manner by suggesting ways in which the salient aspects of their interpretation, that is, (the specifics of) their modality, their subject interpretation, and their illocutionary use, could be derived from the interpretively relevant properties of their form.Earlier versions of this paper were presented at the Zentrum für Allgemeine Sprachwissenschaft, Typologie und Universalienforschung-Berlin (3/02, 5/02), the University of Pennsylvania (4/02), and the University of Frankfurt (6/02). Thanks to all the audiences for valuable comments and suggestions. Special thanks for constructive discussion and help with specific points of the paper are owed to many: Rajesh Bhatt, Veronika Ehrich, Ewald Lang, Manfred Krifka, Ingo Reich, Inger Rosengren, Joachim Sabel, Hubert Truckenbrodt, Ede Zimmermann, Ilse Zimmermann as well as the editor, Mark Louden, and two anonymous referees. A preprint version of this paper (here considerably revised) appeared as Reis 2002.
A morphological analysis of marsupial mammal higher‐level phylogenetic relationships
2003-06-01

Abstract Phylogenetic relationships among marsupial taxa have proven to be more complex than the simple grouping of species by continent. Recent marsupials are distributed across the New World, Australia, New Guinea, and certain neighboring islands. Morphological characteristics of various groups bridge different geographical areas. We investigated the origin of these characteristics by assembling a morphological data matrix consisting of a new suite of 149 postcranial characters and incorporated a series of previously published data on the craniodental (76 characters) and soft tissue (5 characters) anatomy. Twenty‐one marsupial terminal taxa representing all the major radiations of marsupials and 10 outgroups, most of which are exceptionally well‐preserved fossils such as Vincelestes , Ukhaatherium , and a few basal metatherian taxa, were investigated. A maximum parsimony analysis was conducted, resulting in one most parsimonious tree. Relationships among outgroups are congruent with current understanding of mammalian phylogeny. All currently accepted marsupial orders were recovered by the analysis. We confirmed previous results showing the South American “monito del monte” Dromiciops nested within the Australasian radiation. Within this australidelphian clade, Dromiciops was closely allied with the Diprotodontia. The South American paucituberculates appeared more closely related to the Australidelphia than to the American Didelphimorphia. The marsupial mole Notoryctes and the Peramelia were closely allied to each other and in turn were the sister group of the Dromiciops plus Diprotodontia clade. This pattern of relationships left Dasyuromorphia as the most basal offshoot of the Australidelphia. Whereas this tree topology recovers some signal that had been detected by previous studies, morphological and/or molecular, some novel hypotheses are also supported.
A Randomized Clinical Trial Comparing Breakfast, Dinner, or Bedtime Administration of Insulin Glargine in Patients With Type 1 Diabetes
2003-06-01

OBJECTIVE—Insulin glargine (Lantus), a long-acting human insulin analog, provides effective glycemic control when administered at bedtime. This open-label, randomized, parallel group, multicenter study investigated whether insulin glargine is equally effective if administered before breakfast, before dinner, or at bedtime. RESEARCH DESIGN AND METHODS—Patients with type 1 diabetes on basal-bolus therapy (n = 378, 18–68 years, HbA1c 5.5–9.8%) were treated with once-daily individually titrated insulin glargine in combination with prandial insulin lispro for 24 weeks. RESULTS—Baseline characteristics were similar in the three groups (overall age 40.9 ± 11.9 years, diabetes duration 17.3 ± 11.5 years). Median total daily insulin dose was similar at baseline (0.65, 0.65, and 0.66 IU/kg for breakfast, dinner, and bedtime, respectively) and remained relatively constant over the study period; however, the insulin glargine–to–total insulin dose ratio increased more in the breakfast group than in the dinner and bedtime groups. A similar reduction of adjusted mean HbA1c from baseline to end point occurred in all patients (7.6–7.4, 7.6–7.5, and 7.6–7.5% for breakfast, dinner, and bedtime, respectively), and a similar percentage achieved HbA1c &amp;lt;7.0% at end point in all groups (29.5, 29.8, and 25.8%, respectively). The 24-h blood glucose profiles in relation to injection time were similar in all groups. The incidences of total symptomatic and severe hypoglycemia did not differ between the three treatment groups; however, nocturnal hypoglycemia occurred in significantly fewer patients in the breakfast group (59.5%) compared with the dinner (71.9%) and bedtime (77.5%) groups (P = 0.005). CONCLUSIONS—These data suggest that insulin glargine, in combination with insulin lispro, is safe and effective when administered before breakfast, before dinner, or at bedtime.