Effects of an S84E mutation of bovine growth hormone in transgenic mice

The ability of mutant bovine growth hormones (bGH) to serve as either agonist or antagonist has been demonstrated in transgenic mice. We have prepared two transgenic strains of FVB/N mice, one expressing wild-type bGH and a second with a glutamic acid mutation at serine 84 in helix 2. Comparison of their phenotypes to those of nontransgenic littermates indicates that wild-type bGH induces a previously described phenotype for hyper-somatotrophic mice. In contrast, the replacement of the side chain hydroxyl at serine 84 with acetic acid produced a phenotype that expressed bGH at appreciable concentrations, but failed to elicit the phenotype observed with either an agonist or an antagonist of bGH. These results indicate that serine 84 is crucial for the activity of bGH despite this site being distal to the receptor binding surfaces.     

European guidelines for quality assurance in cervical cancer screening: recommendations for collecting samples for conventional and liquid-based cytology.

The current paper presents an annex in the second edition of the European Guidelines for Quality Assurance in Cervical Cancer Screening. It provides guidance on how to make a satisfactory conventional Pap smear or a liquid-based cytology (LBC) sample. Practitioners taking samples for cytology should first explain to the woman the purpose, the procedure and how the result will be communicated. Three sampling methods are considered as acceptable for preparing conventional Pap smears: (i) the cervical broom; (ii) the combination of a spatula and an endocervical brush; and (iii) the extended tip spatula. Smear takers should take care to sample the entire circumference of the transformation zone, to quickly spread the cellular material over a glass slide, and to fix the preparation within a few seconds to avoid drying artefacts. According to local guidelines, one of these three methods may be preferred. Sampling with a cotton tip applicator is inappropriate. Similar procedures should be followed for sampling cells for LBC, but only plastic devices may be used. The collected cells should be quickly transferred into a vial with fixative liquid according to the instructions of the manufacturer of the LBC system. Subsequently, the slide or vial and the completed request form are sent to the laboratory for cytological interpretation.     

Rem sleep without atonia--from cats to humans

Basic science research observations often lead to unexpected surprises. It is likely that in 1965 when Dr. Michel Jouvet placed bilateral peri-locus coeruleus lesions in cats and observed REM sleep without atonia (RWA) and "oneiric" behavior that could only be explained by "acting out dreams" (or "dreaming out acts"), he recognized that it was an important observation, but had little inkling of its true significance. Nor could he even imagine that it would lead to such greater understanding of wake/sleep phenomena in humans. Likely also, the first observation of REM sleep behavior disorder (RBD) in humans was felt to be interesting and novel - again with no true appreciation of what this seemingly simple observation would lead to important clinical relationships with numerous neurodegenerative disorders. The identification of RBD in humans also buttressed the concept of state dissociation, which has served to explain many previously unexplainable human behavioral phenomena.     

NUFIP1 (nuclear FMRP interacting protein 1) is a nucleocytoplasmic shuttling protein associated with active synaptoneurosomes

Fragile X syndrome, the most common cause of inherited mental retardation, is caused by the absence of FMRP (Fragile X Mental Retardation Protein). FMRP is an RNA binding protein reported to be involved in translational control, notably at postsynaptic sites of protein synthesis as a part of a multiprotein/mRNA complex. One of the FMRP interactors, NUFIP1, is an RNA binding protein with an expression profile matching that of FMRP. We now show that in the nucleus NUFIP1 is localized in the nuclear matrix in RNA-containing structures lying in the proximity of, but not overlapping with, sites of nascent RNA. NUFIP1 is also present in the cytoplasm, where it is associated with ribosomes, similarly to FMRP. In neurons NUFIP1 can be detected in functional synaptoneurosomes, colocalizing with ribosomes. Consistent with its subcellular localization in both nucleus and cytoplasm, we show that NUFIP1 contains a functional CRM1-dependent nuclear export signal and is able to shuttle between these two cellular compartments. These findings suggest the involvement of NUFIP1 in the export and localization of mRNA and, in association with FMRP, in the regulation of local protein synthesis near synapses.     

Highly skewed sex ratios in the critically endangered Taita thrush as revealed by CHD genes

The study of sex-ratio patterns in threatened bird species has yielded crucial information with regard to their conservation and management. In the case of sexually monomorphic species, i.e. species that cannot be sexed by their appearance, DNA-based sexing techniques are increasingly applied. We present data on the sexing of adult Taita thrushes, a critically endangered forest endemic from south-east Kenya. In addition to describing a morphometric trait that can be used to sex individuals directly upon capture, we comment on a remarkable skew in sex ratio that might have important consequences for the long-term survival of the species.     

A review of the Pterogeniidae (Goleoptera)

The Pterogeniidae, a family of beetles from Indoaustralia, are revised. They comprise five genera and 24 species. Three genera and 17 species are described as new and one species is synonymized. It is shown that the male and particularly the female genitalia provide useful means for species definition. The phylogenetic relationships are discussed based on a cladistic analysis of 23 morphological characters using PAUP. The analysis resulted in a single cladogram with following grouping: ( Kryptogenius + ( Tychogenius + ( Katagenius + ( Plerogenins + Histanocerus )))). For rooting the cladogram and polarizing the characters, Sivacrypticus indicus (Archeocrypticidae) was used as an outgroup. The majority of the species is restricted to insular tropical Asia and Oceania but four of them extend their range onto the Malayan Peninsula. Another four species are known only from continental Asia, i.e. two species from South India and one each from Malayan Peninsula and Vietnam respectively. Species of Kryptogenius, Pterogenius, Katagenius and Tychogenius are highly endemic and could therefore potentially be useful for analysing areas of endemism. For this, however, the cladistic relationships should be resolved at species level. Species of Histanocerus are more widely distributed but none is found on both sides of Wallace's line.     

Increased Sporulation of Vesicular-Arbuscular Mycorrhizal Fungi by Manipulation of Nutrient Regimens

Adjustment of pot culture nutrient solutions increased root colonization and sporulation of vesicular-arbuscular mycorrhizal (VAM) fungi. Paspalum notatum Flugge and VAM fungi were grown in a sandy soil low in N and available P. Hoagland nutrient solution without P enhanced sporulation in soil and root colonization of Acaulospora longula, Scutellospora heterogama, Gigaspora margarita, and a wide range of other VAM fungi over levels produced by a tap water control or nutrient solutions containing P. However, Glomus intraradices produced significantly more spores in plant roots in the tap water control treatment. The effect of the nutrient solutions was not due solely to N nutrition, because the addition of NH₄NO₃ decreased both colonization and sporulation by G. margarita relative to levels produced by Hoagland solution without P.     

Differential effects of protein kinase C on the levels of epithelial Na+ channel subunit proteins

Regulation of epithelial Na(+) channel (ENaC) subunit levels by protein kinase C (PKC) was investigated in A6 cells. PKC activation altered ENaC subunit levels, differentially decreasing the levels of both beta and gamma, but not alphaENaC. Temporal regulation of beta and gammaENaC by PKC differed; gammaENaC decreased with a time constant of 3.7 +/- 1.0 h, whereas betaENaC decreased in 13.9 +/- 3. 0 h. Activation of PKC also resulted in a decrease in trans-epithelial Na(+) reabsorption for up to 48 h. PMA activation of PKC resulted in negative feedback inhibition of PKC protein levels beginning within 4 h. Both beta and gammaENaC levels, as well as transport tended toward pretreatment values after 48 h of PMA treatment. PKC inhibitors attenuated the effects of PMA on ENaC subunit levels and Na(+) transport. These results directly show for the first time that PKC differentially regulates ENaC subunit levels by decreasing the levels of beta and gamma but not alphaENaC protein. These results imply a PKC-dependent, long term decrease in Na(+) reabsorption.     

Learning visuomotor transformations for gaze-control and grasping

For reaching to and grasping of an object, visual information about the object must be transformed into motor or postural commands for the arm and hand. In this paper, we present a robot model for visually guided reaching and grasping. The model mimics two alternative processing pathways for grasping, which are also likely to coexist in the human brain. The first pathway directly uses the retinal activation to encode the target position. In the second pathway, a saccade controller makes the eyes (cameras) focus on the target, and the gaze direction is used instead as positional input. For both pathways, an arm controller transforms information on the target’s position and orientation into an arm posture suitable for grasping. For the training of the saccade controller, we suggest a novel staged learning method which does not require a teacher that provides the necessary motor commands. The arm controller uses unsupervised learning: it is based on a density model of the sensor and the motor data. Using this density, a mapping is achieved by completing a partially given sensorimotor pattern. The controller can cope with the ambiguity in having a set of redundant arm postures for a given target. The combined model of saccade and arm controller was able to fixate and grasp an elongated object with arbitrary orientation and at arbitrary position on a table in 94% of trials.     

Physical interactions of static magnetic fields with living tissues

Clinical magnetic resonance imaging (MRI) was introduced in the early 1980s and has become a widely accepted and heavily utilized medical technology. This technique requires that the patients being studied be exposed to an intense magnetic field of a strength not previously encountered on a wide scale by humans. Nonetheless, the technique has proved to be very safe and the vast majority of the scans have been performed without any evidence of injury to the patient. In this article the history of proposed interactions of magnetic fields with human tissues is briefly reviewed and the predictions of electromagnetic theory on the nature and strength of these interactions are described. The physical basis of the relative weakness of these interactions is attributed to the very low magnetic susceptibility of human tissues and the lack of any substantial amount of ferromagnetic material normally occurring in these tissues. The presence of ferromagnetic foreign bodies within patients, or in the vicinity of the scanner, represents a very great hazard that must be scrupulously avoided. As technology and experience advance, ever stronger magnetic field strengths are being brought into service to improve the capabilities of this imaging technology and the benefits to patients. It is imperative that vigilance be maintained as these higher field strengths are introduced into clinical practice to assure that the high degree of patient safety that has been associated with MRI is maintained.