Miracle-dz/UniFAR-FTUs huggingface dataset:
THE POSSIBLE RELATIONSHIP BETWEEN ACROMEGALY AND DIABETES: WITH REPORT OF THREE CASES

According to the figures given by various authors, diabetes occurs in from 10 to 40 per cent of the cases of acromegaly. Even the lowest of these figures is sufficiently high to suggest that this is more than a coincidence, that there must be some common factor underlying both conditions. In going over the older literature one finds that most of the diagnoses of diabetes in these cases have been made on the basis of the urinary examinations for sugar. In considering this subject, therefore, we must bear this point in mind for in the light of more recent work we know that glycosuria is not always a true indication of diabetes. In an analysis of all cases of pituitary disease which have been seen at the Cleveland Clinic, comprising forty-one cases to date, seven cases of acromegaly were found, diabetes being present in two of these, 28.5 per cent.
Tonic activation of group I mGluRs modulates inhibitory synaptic strength by regulating KCC2 activity

The furosemide‐sensitive potassium–chloride cotransporter (KCC2) plays an important role in establishing the intracellular chloride concentration in many neurons within the central nervous system. Consequently, modulation of KCC2 function will regulate the reversal potential for synaptic GABAergic inputs, thus setting the strength of inhibitory transmission. We show that tonic activation of group I metabotropic glutamate receptors (mGluR1s) regulates inhibitory synaptic strength via modulation of KCC2 function in pyramidal neurons of the hippocampal CA3 area. Specifically, group I mGluRs signal via activation of a protein kinase C‐dependent pathway to alter KCC2 activity, thereby altering the intracellular chloride concentration, and thus inhibitory synaptic input. This interaction between the glutamatergic and chloride transport systems highlights a novel homeostatic mechanism whereby ambient glutamate levels directly regulate the inhibitory synaptic tone by setting the activity level of KCC2. Thus, mGluRs are poised to play a pivotal role in providing a direct interplay between the excitatory and inhibitory systems in the hippocampus.
Cellular mechanism of the voltage‐dependent change in slow potentials generated in circular smooth muscle of the guinea‐pig gastric corpus

The cellular mechanism of the voltage‐dependent properties of slow potentials were investigated in single bundles of circular smooth muscle isolated from the gastric corpus of guinea‐pig using conventional microelectrode recordings. Hyperpolarization of the membrane by current injection decreased the frequency and increased the amplitude of slow potentials linearly. At potentials negative of −80 mV, slow potential generation was abolished and a periodic generation of clustered unitary potentials was evident. Application of cyclopiazonic acid (CPA, 20 μm) or thapsigargin (1 μm; inhibitors of Ca2+‐ATPase), carbonyl cyanide m‐chlorophenyl hydrazone (CCCP, 0.1 μm; mitochondrial protonophore) or 2‐aminoethoxydiphenyl borate (2‐APB, 20 μm; inhibitor of IP3 receptor‐mediated Ca2+ release) depolarized the membrane and reduced or inhibited the amplitude and frequency of slow potentials: repolarization of the membrane to the resting level by current injection resulted in a recovery of the amplitude of slow potentials in the presence of CPA or CCCP, but not 2‐APB. The slow potentials abolished by thapsigargin did not recover upon membrane repolarization. The altered frequency of slow potentials by 2‐APB, CPA or CCCP was not reversed by membrane repolarization to control potentials. Depolarization of the membrane by about 10 mV with high‐potassium solution also reduced the amplitude and increased the frequency of slow potentials in a manner restored by repolarization to control potentials upon current injection, suggesting that membrane depolarization did not affect the voltage dependency of pacemaker activity. The results indicate that in corpus circular muscles the voltage dependency of the frequency and amplitude of slow potentials requires a functional Ca2+ store and mitochondria.
STIM1–Orai1 interactions and Orai1 conformational changes revealed by live‐cell FRET microscopy

Ca2+ entry through store‐operated Ca2+ release‐activated Ca2+ (CRAC) channels initiates key functions such as gene expression and exocytosis of inflammatory mediators. Activation of CRAC channels by store depletion involves the redistribution of the ER Ca2+ sensor, stromal interaction molecule 1 (STIM1), to peripheral sites where it co‐clusters with the CRAC channel subunit, Orai1. However, how STIM1 communicates with the CRAC channel and initiates the subsequent events culminating in channel opening is unclear. Here, we show that redistribution of STIM1 and Orai1 occurs in parallel with a pronounced increase in fluorescence resonance energy transfer (FRET) between STIM1 and Orai1, supporting the idea that activation of CRAC channels occurs through physical interactions with STIM1. Co‐expression of Orai1–CFP and Orai1–YFP results in a high degree of FRET in resting cells, indicating that Orai1 exists as a multimer. However, store depletion triggers molecular rearrangements in Orai1 resulting in a decline in Orai1–Orai1 FRET. The decline in Orai1–Orai1 FRET is not seen in the absence of STIM1 co‐expression and is abolished in Orai1 mutants with impaired STIM1 interaction. Both the STIM1–Orai1 interaction as well as the molecular rearrangements in Orai1 are altered by two powerful modulators of CRAC channel activity: extracellular Ca2+ and 2‐APB. These studies identify a STIM1‐dependent conformational change in Orai1 during the activation of CRAC channels and reveal that STIM1–Orai1 interaction and the downstream Orai1 conformational change can be independently modulated to fine‐tune CRAC channel activity.
Roles of axonal sodium channels in precise auditory time coding at nucleus magnocellularis of the chick

How the axonal distribution of Na+ channels affects the precision of spike timing is not well understood. We addressed this question in auditory relay neurons of the avian nucleus magnocellularis. These neurons encode and convey information about the fine structure of sounds to which they are tuned by generating precisely timed action potentials in response to synaptic inputs. Patterns of synaptic inputs differ as a function of tuning. A small number of large inputs innervate high‐ and middle‐frequency neurons, while a large number of small inputs innervate low‐frequency neurons. We found that the distribution and density of Na+ channels in the axon initial segments varied with the synaptic inputs, and were distinct in the low‐frequency neurons. Low‐frequency neurons had a higher density of Na+ channels within a longer axonal stretch, and showed a larger spike amplitude and whole‐cell Na+ current than high/middle‐frequency neurons. Computer simulations revealed that for low‐frequency neurons, a large number of Na+ channels were crucial for preserving spike timing because it overcame Na+ current inactivation and K+ current activation during compound EPSPs evoked by converging small inputs. In contrast, fewer channels were sufficient to generate a spike with high precision in response to an EPSP induced by a single massive input in the high/middle‐frequency neurons. Thus the axonal Na+ channel distribution is effectively coupled with synaptic inputs, allowing these neurons to convey auditory information in the timing of firing.
Where the O2 goes to: preservation of human fetal oxygen delivery and consumption at high altitude

Fetal growth is decreased at high altitude (> 2700 m). We hypothesized that variation in fetal O2 delivery might account for both the altitude effect and the relative preservation of fetal growth in multigenerational natives to high altitude. Participants were 168 women of European or Andean ancestry living at 3600 m or 400 m. Ancestry was genetically confirmed. Umbilical vein blood flow was measured using ultrasound and Doppler. Cord blood samples permitted calculation of fetal O2 delivery and consumption. Andean fetuses had greater blood flow and oxygen delivery than Europeans and weighed more at birth, regardless of altitude (+208 g, P < 0.0001). Fetal blood flow was decreased at 3600 m (P < 0.0001); the decrement was similar in both ancestry groups. Altitude‐associated decrease in birth weight was greater in Europeans (−417 g) than Andeans (−228 g, P < 0.005). Birth weight at 3600 m was > 200 g lower for Europeans at any given level of blood flow or O2 delivery. Fetal haemoglobin concentration was increased, decreased, and the fetal / curve was left‐shifted at 3600 m. Fetuses receiving less O2 extracted more (r2= 0.35, P < 0.0001). These adaptations resulted in similar fetal O2 delivery and consumption across all four groups. Increased umbilical venous O2 delivery correlated with increased fetal O2 consumption per kg weight (r2= 0.50, P < 0.0001). Blood flow (r2= 0.16, P < 0.001) and O2 delivery (r2= 0.17, P < 0.001) correlated with birth weight at 3600 m, but not at 400 m (r2= 0.04, and 0.03, respectively). We concluded that the most pronounced difference at high altitude is reduced fetal blood flow, but fetal haematological adaptation and fetal capacity to increase O2 extraction indicates that deficit in fetal oxygen delivery is unlikely to be causally associated with the altitude‐ and ancestry‐related differences in fetal growth.
Maximising reference services in a pharmaceutical R&D library

November 1998 marked the beginning of a new Reference Services function for SmithKline Beecham (SB) Pharmaceuticals Research and Development (R&D) Library Services Group. After a number of years of excellent but inconsistent service at the multiple site libraries within SB R&D, and no formal reference service available at many of those sites, a period of planning and training has resulted in the ability to provide a consistent, transnational service to all customer groups within R&D, improve access to Reference Services and also provide a measured and timely service. Reference Services has striven to make the best use of Web resources that are available through the Internet and intranet, including using external Web sites to answer enquiries and also creating our own Web pages in order to facilitate access to resources.
Editorial Board.

The actual development of the media has imposed new professional standards and an intensive practice on the part of media staff and reporters. However, all their activity can’t escape the evolving questions: What position must they take up on the event offered to the public opinion? What are the expected consequences of a published or broadcasted story? The raising of the questions above brings the debate about the motives standing behind the journalists or media people behaviour to the discussion table; the debate on ethic reasoning or the applied ethic principles, through which, a certain decision can be reached. This aspect of the media’s activity is called in a moment when media has become the fourth most influential power, and media people relate with leading and decision-making structures of the society. In fact, they see themselves as part of those structures. Many researchers tend to believe that pragmatism is prevailing in today’s world-wide media, and ethic codes are less accepted; while anarchy is more preferred. But the role and power of media makes the need for ethic principles indispensable. This need is considered and well understood only when media professionals are aware of the importance of their profession, role, mission, and impact on the public opinion. Media presents the level and situation of the society. Media changes also when the society is under change. In the moments of change or deep transformation, media runs to present all the events, and often pretends to be an arbitrator of the truth. In this context, media positions itself either in deeply opposing journalism or in deeply defending journalism. Only by avoiding these extreme positions and acting always in accordance with public opinion interest will it be possible to create an ethic atmosphere where everyone is involved: old generations that have reached a certain level of ethics because of their work experience, and the new generations which are less wiling to consider this very important issue. When ethics gains terrain, the gap between professional practice and serious media behaviour studies will be narrowed. Wide and persisting discussions within media circles or institutions are contributing to the creation of an ethic way of thinking and an essential ethics atmosphere. However, this cannot be induced only by compiling or reading ethics codes. Beside codes, an effective way of creating this atmosphere is to intertwine ethic principles with everyday practiced professional standards and the communication skills of reporters and editors.
Developing Transformational Leadership: 1992 and Beyond

European management must become more transformational with respect to its leadership if it is to address the challenges confronting the European community after 1992. The question arises, can transformational leadership be trained? The answer is affirmative. A number of successful training experiences in North America are described in this article. These experiences form the basis for a prototype training programme now being conducted in a large European conglomerate at the junior, middle and senior management level. A general overview of these programmes are provided, as well as evidence that they are having strong beneficial effects on the participants in the workshops, and in their performance back on their jobs.
Whither the hypercolumn?

Among the crowning achievements of Hubel and Wiesel's highly influential studies on primary visual cortex is the description of the cortical hypercolumn, a set of cortical columns with functional properties spanning a particular parameter space. This fundamental concept laid the groundwork for the notion of a modular sensory cortex, canonical cortical circuits and an understanding of visual field coverage beyond simple retinotopy. Surprisingly, the search for and description of analogous hypercolumnar organizations in other cortical areas to date has been limited. In the present work, we have applied the hypercolumn concept to the functional organization of the second visual area, V2. We found it important to separate out the original definition of the hypercolumn from other associated observations and concepts, not all of which are applicable to V2. We present results indicating that, as in V1, the V2 hypercolumns for orientation and binocular interaction (disparity) run roughly orthogonal to each other. We quantified the ‘nearest neighbour’ periodicities for the hypercolumns for ocular dominance, orientation, colour and disparity, and found a marked similarity in the periodicities of all of these hypercolumns, both across hypercolumn type and across visual areas V1 and V2. The results support an underlying common mechanism that constrains the anatomical extent of hypercolumn systems, and highlight the original definition of the cortical hypercolumn.
Facteurs de risque de démence dans une population de personnes âgées sénégalaises

Description La demence est devenue un probleme de sante publique. Dans le but d’une prevention, il est important de connaitre son epidemiologie au Senegal. L’objectif de cette etude etait d’identifier les facteurs de risque de demence dans une population de personnes âgees senegalaises. Methodes Une etude transversale a ete realisee du 01 Mars 2004 au 31 Decembre 2005 aupres d’une population de 872 personnes âgees de 55ans et plus utilisant le Centre Medicosocial et Universitaire de l’Institut de Prevoyance Retraite du Senegal pour des soins. Par une etude en deux phases, des donnees sociodemographiques, sur le mode de vie, le reseau social, les antecedents ont ete collectees a l’aide d’un questionnaire structure complete par un examen clinique et une evaluation neuropsychologique. Le diagnostic de demence reposait sur des criteres DSM IV-R.
Fuel selection in Wistar rats exposed to cold: shivering thermogenesis diverts fatty acids from re‐esterification to oxidation

This study characterizes the effects of shivering thermogenesis on metabolic fuel selection in Wistar rats. Because lipids account for most of the heat produced, we have investigated: (1) whether the rate of appearance of non‐esterified fatty acids (Ra NEFAs) is stimulated by shivering, (2) whether mono‐unsaturated (oleate) and saturated fatty acids (palmitate) are affected similarly, and (3) whether the partitioning between fatty acid oxidation and re‐esterification is altered by cold exposure. Fuel oxidation was measured by indirect calorimetry and fatty acid mobilization by continuous infusion of 9,10‐[3H]oleate and 1‐[14C]palmitate. During steady‐state cold exposure, results show that total heat production is unequally shared by the oxidation of lipids (52% of metabolic rate), carbohydrates (35%) and proteins (13%), and that the same fuel selection pattern is observed at all shivering intensities. All previous research shows that mammals stimulate Ra NEFA to support exercise or shivering. In contrast, results reveal that the Ra NEFA of the rat remains constant during cold exposure (∼55 μmol kg−1 min−1). No preferential use of mono‐unsaturated over saturated fatty acids could be demonstrated. The rat decreases its rate of fatty acid re‐esterification from 48.4 ± 6.4 to 19.6 ± 6.3 μmol kg−1 min−1 to provide energy to shivering muscles. This study is the first to show that mammals do not only increase fatty acid availability for oxidation by stimulating Ra NEFA. Reallocation of fatty acids from re‐esterification to oxidation is a novel, alternative strategy used by the rat to support shivering.
Rapid actions of oestrogen on gonadotropin‐releasing hormone neurons; from fantasy to physiology?

Oestradiol (E2) exerts critical homeostatic feedback effects upon gonadotropin‐releasing hormone (GnRH) neurons to maintain fertility. In the female, E2 has both negative and positive feedback actions to suppress and stimulate GnRH neuron activity at different times of the ovarian cycle. This review summarizes reported rapid E2 effects on native embryonic and adult GnRH neurons and attempts to put them into a physiological perspective. Oestrogen has been shown to rapidly modulate multiple processes in embryonic and adult GnRH neurons including intracellular calcium levels, electrical activity and specific second messenger pathways, as well as GnRH secretion itself. Evaluation of in vivo data suggests that there is no essential role for rapid E2 actions in the positive feedback mechanism but that they may comprise part of the negative feedback pathway. Adult GnRH neurons are only likely to be exposed to E2 from the gonads via the circulation with appropriate physiological E2 concentrations in the rodent being 10–50 pm for negative feedback ranging up to 400 pm for positive feedback. Although most studies to date have examined the effects of supraphysiological E2 levels on GnRH neurons, there is accumulating evidence that rapid E2 actions may have a physiological role in suppressing GnRH neuron activity.
The effects of attachment and outness on illness adjustment among gay men with prostate cancer

Previous research has suggested that gay men facing prostate cancer may be particularly vulnerable to poor illness adjustment. Moreover, although attachment and greater disclosure of sexual orientation have been associated with health outcomes, their associations in this population have been largely unexamined. The purpose of the present study was to investigate whether greater outness about one's sexual orientation significantly mediated the associations between anxious and avoidant attachment and illness intrusiveness among gay men with prostate cancer.
One-parameter families of bivariate distributions with fixed marginals

For artibrary absolutely continuous univariate distributions F and G we discuss the problem of generating one-parameter families of bivarlate distributions With fixed marginals F and G. According to the statistical literature, for fixed F and G Caere are known co axist only two such families Which satisfy the conditions that they contain the Fee bounds and the distribution corresponding so independent random variables. This paper formalises the problem by suggesting twoadditional conditions these families should satisfy and shows that it is easy to generate many such one-parameter familie In particular, one new family is presented.
The Anrep effect requires transactivation of the epidermal growth factor receptor

Myocardial stretch elicits a biphasic contractile response: the Frank–Starling mechanism followed by the slow force response (SFR) or Anrep effect. In this study we hypothesized that the SFR depends on epidermal growth factor receptor (EGFR) transactivation after the myocardial stretch‐induced angiotensin II (Ang II)/endothelin (ET) release. Experiments were performed in isolated cat papillary muscles stretched from 92 to 98% of the length at which maximal twitch force was developed (Lmax). The SFR was 123 ± 1% of the immediate rapid phase (n= 6, P < 0.05) and was blunted by preventing EGFR transactivation with the Src‐kinase inhibitor PP1 (99 ± 2%, n= 4), matrix metalloproteinase inhibitor MMPI (108 ± 4%, n= 11), the EGFR blocker AG1478 (98 ± 2%, n= 6) or the mitochondrial transition pore blocker clyclosporine (99 ± 3%, n= 6). Stretch increased ERK1/2 phosphorylation by 196 ± 17% of control (n= 7, P < 0.05), an effect that was prevented by PP1 (124 ± 22%, n= 7) and AG1478 (131 ± 17%, n= 4). In myocardial slices, Ang II (which enhances ET mRNA) or endothelin‐1 (ET‐1)‐induced increase in O2− production (146 ± 14%, n= 9, and 191 ± 17%, n= 13, of control, respectively, P < 0.05) was cancelled by AG1478 (94 ± 5%, n= 12, and 98 ± 15%, n= 8, respectively) or PP1 (100 ± 4%, n= 6, and 99 ± 8%, n= 3, respectively). EGF increased O2− production by 149 ± 4% of control (n= 9, P < 0.05), an effect cancelled by inhibiting NADPH oxidase with apocynin (110 ± 6%n= 7), mKATP channels with 5‐hydroxydecanoic acid (5‐HD; 105 ± 5%, n= 8), the respiratory chain with rotenone (110 ± 7%, n= 7) or the mitochondrial permeability transition pore with cyclosporine (111 ± 10%, n= 6). EGF increased ERK1/2 phosphorylation (136 ± 8% of control, n= 9, P < 0.05), which was blunted by 5‐HD (97 ± 5%, n= 4), suggesting that ERK1/2 activation is downstream of mitochondrial oxidative stress. Finally, stretch increased Ser703 Na+/H+ exchanger‐1 (NHE‐1) phosphorylation by 172 ± 24% of control (n= 4, P < 0.05), an effect that was cancelled by AG1478 (94 ± 17%, n= 4). In conclusion, our data show for the first time that EGFR transactivation is crucial in the chain of events leading to the Anrep effect.