Chromatin preferences of the perichromosomal layer constituent pKi-67

The proliferation-associated nuclear protein pKi-67 relocates from the nucleolus to the chromosome surface during the G2/M transition of the cell cycle and contributes to the formation of the perichromosomal layer. We investigated the in-vivo binding preferences of pKi-67 for various chromatin blocks of the mitotic chromosomes from the human and two mouse species, Mus musculus and M. caroli. All chromosomes were decorated with pKi-67 but displayed a gap of pKi-67 decoration in the centromere and NOR regions. pKi-67 distribution in a rearranged mouse chromosome showed that the formation of the centromeric gap was controlled by the specific chromatin in that region. While most chromatin served as a substrate for direct or indirect binding of pKi-67, we identified three types of chromatin that bound less or no pKi-67. These were: (1) the centromeric heterochromatin defined by the alpha satellite DNA in the human, by the mouse minor satellite in M. musculus and the 60- and 79-bp satellites in M. caroli; (2) the pericentromeric heterochromatin in M. musculus defined by the mouse major satellite, and (3) NORs in the human and in M. musculus defined by rDNA repeats. In contrast, the conspicuous blocks of pericentromeric heterochromatin in human chromosomes 1, 9 and 16 containing the 5-bp satellite showed intense pKi-67 decoration. The centromeric gap may have a biological significance for the proper attachment of the chromosomes to the mitotic spindle. In this context, our results suggest a new role for centromeric heterochromatin: the control of the centromeric gap in the perichromosomal layer.     

The Gene for Ciliary Neurotrophic Factor (CNTF) Maps to Murine Chromosome 19 and its Expression is Not Affected in the Hereditary Motoneuron Disease 'Wobbler' of the Mouse

The cDNA for ciliary neurotrophic factor (CNTF), a polypeptide involved in the survival of motoneurons in mammals, has recently been cloned (Stöckli et al., Nature, 342 , 920–923, 1989; Lin et al Science, 246 , 1023–1025, 1989). We have now localized the corresponding gene Cntf to chromosome 19 in the mouse, using an interspecific cross between Mus spretus and Mus musculus domesticus. The latter was carrying the gene wobbler (wr) for spinal muscular atrophy. DNA was prepared from backcross individuals and typed for the segregation of species-specific Cntf restriction fragments in relation to DNA markers of known chromosomal location. The M.spretus allele of Cntf cosegregated with chromosome 19 markers and mapped closely to Ly-1 to a region of mouse chromosome 19 with conserved synteny to human chromosome 11q. Cntf is not linked to wr, and the expression of CNTF mRNA and protein appears close to normal in facial and sciatic nerves of affected (wr/wr) mice, suggesting that motoneuron degeneration of wobbler mice has its origin in defects other than reduced CNTF expression.     

Dissecting innate immunity by germline mutagenesis

The innate arm of our immune system is the first line of defence against infections. In addition, it is believed to drive adaptive immune responses, which help fight pathogens and provide long-term memory. As such, the innate immune system is instrumental for protection against pathogens that would otherwise destroy their host. Although our understanding of the innate immune components involved in pathogen sensing and fighting is improving, it is still limited. This is particularly exemplified by increased documentation of innate immune deficiencies in humans that often result in high and recurrent susceptibility to infections or even death, without the genetic cause being evident. To provide further insight into the mechanisms by which pathogen sensing and eradication occur, several strategies can be used. The current review focuses on the forward genetic approaches that have been used to dissect innate immunity in the fruit fly and the mouse. For both animal models, forward genetics has been instrumental in the deciphering of innate immunity and has greatly improved our understanding of how we respond to invading pathogens.     

Crystal structure of the Mus81-Eme1 complex

The Mus81-Eme1 complex is a structure-specific endonuclease that plays an important role in rescuing stalled replication forks and resolving the meiotic recombination intermediates in eukaryotes. We have determined the crystal structure of the Mus81-Eme1 complex. Both Mus81 and Eme1 consist of a central nuclease domain, two repeats of the helix-hairpin-helix (HhH) motif at their C-terminal region, and a linker helix. While each domain structure resembles archaeal XPF homologs, the overall structure is significantly different from those due to the structure of a linker helix. We show that a flexible intradomain linker that formed with 36 residues in the nuclease domain of Eme1 is essential for the recognition of DNA. We identified several basic residues lining the outer surface of the active site cleft of Mus81 that are involved in the interaction with a flexible arm of a nicked Holliday junction (HJ). These interactions might contribute to the optimal positioning of the opposite junction across the nick into the catalytic site, which provided the basis for the "nick and counternick" mechanism of Mus81-Eme1 and for the nicked HJ to be the favored in vitro substrate of this enzyme.     

Pain reduction by infrared light-emitting diode irradiation: a pilot study on experimentally induced delayed-onset muscle soreness in humans

The present pilot study investigated the analgesic efficacy of light-emitting diode (LED). In view of a standardised and controlled pain reduction study design, this in vivo trial was conducted on experimentally induced delayed-onset muscle soreness (DOMS). Thirty-two eligible human volunteers were randomly assigned to either an experimental (n=16) or placebo group (n=16). Immediately following the induction of muscle soreness, perceived pain was measured by means of a visual analog scale (VAS), followed by a more objective mechanical pain threshold (MPT) measurement and finally an eccentric/concentric isokinetic peak torque (IPT) assessment. The experimental group was treated with infrared LED at one of both arms, the other arm served as control. Irradiation lasted 6 min at a continuous power output of 160 mW, resulting in an energy density of 3.2 J/cm². The subjects of the placebo group received sham irradiation at both sides. In post-treatment, a second daily assessment of MPT and VAS took place. The treatment and assessment procedure (MPT, VAS and IPT) was performed during 4 consecutive days. Statistical analysis (a general linear model followed by post hoc least significant difference) revealed no apparent significant analgesic effects of LED at the above-described light parameters and treatment procedure for none of the three outcome measures. However, as the means of all VAS and MPT variables disclose a general analgesic effect of LED irradiation in favour of the experimental group, precaution should be taken in view of any clinical decision on LED. Future research should therefore focus on the investigation of the mechanisms of LED action and on the exploration of the analgesic effects of LED in a larger randomised clinical trial and eventually in more clinical settings.     

Multiple selection responses in house mice bidirectionally selected for thermoregulatory nest-building behavior: Crosses of replicate lines

Replicate high-selected, control, and low-selected lines were crossed at generation 46 of bidirectional selection for thermoregulatory nest-building behavior. Previous analysis of the lines at their limits had revealed multiple responses to uniform selection, where each of the four selected lines responded differently to reverse selection (Laffan, 1989). The reciprocal F₁ crosses showed significant heterosis for nest-building behavior compared to the contemporaneous generations of the parental lines. This pattern of heterosis in all three crosses is consistent with the finding that nest-building behavior in each of the four replicate lines had a different genetic basis, in spite of the phenotypic similarity between the two replicate lines in the high and low direction of nesting. This heterosis effect and the larger number of young weaned in all three crosses compared to their respective contemporaneous generation of the parental lines also support earlier findings that larger nests are closely related to fitness.     

Olfactory bulb control of circadian activity rhythm in mice

Ablation of mouse olfactory bulbs lengthened the circadian period of wheel-running activity by 43 min and delayed the onset of entrained activity by 108 min. A transient increase in activity during the light phase of the 12:12 h light-dark photoperiod also occurred following surgery. These disruptions suggest that olfactory systems can modulate mammalian circadian rhythms.     

STRESS IN MICE INCREASES INTRINSIC PENTOBARBITONE SENSITIVITY BY A PREDOMINANTLY PHARMACODYNAMIC MECHANISM

1. Mice were swum for 3 min at room temperature. 2. After this stress 'sleeping time' in response to pentobarbitone was increased by over 70%. 3. Loss of 'righting reflex' occurred in these stressed animals at brain concentrations of pentobarbitone which were 40% lower than those needed for 'sleep' in the unstressed mice, indicating a true increase in sensitivity to the drug. 'Waking' (the return of the righting reflex) occurred at identical levels in both groups. 4. Kinetic analysis showed that the rates of absorption, elimination and transfer between plasma and brain were slower in the swum than in the unswum mice, probably because of the reduced body temperatures produced by the swimming.     

Ventrale aponeurotische Verlängerung des Musculus gastrocnemius

Operationsprinzip Mehrfache, schr?ge Durchtrennung der kr?ftigen, in den Anatomiebüchern meist übergangenen ventralen aponeurotischen Sehnenplatte des Musculus gastrocnemius erlaubt es bei einer mittelgradigen Muskelkontraktur eine ausreichende Muskell?nge durch Faserdehnung wiederherzustellen. Die ventrale aponeurotische Verl?ngerung des Musculus gastrocnemius wurde von Baumann 1980 erstmals angewandt. Sie wurde am Jahreskongre? der Schweizerischen Gesellschaft für Orthop?die 1988 erstmals vorgestellt.      

单侧唇裂降鼻中隔肌的解剖学研究及意义

目的研究单侧完全性唇裂鼻部肌肉缺损与鼻端中线结构移位与畸形的关系。方法将33例正常成人尸体鼻标本与30例单侧完全性唇裂鼻畸形Ⅱ期修复患者的降鼻中隔肌行解剖组织学对比观察。结果证实单侧完全性唇裂患侧降鼻中隔肌缺损。结论因患侧降鼻中隔肌缺损使鼻中线两侧肌力平衡破坏,肌力平衡失调导致唇裂鼻鼻端中线结构的移位和畸形可能是单侧唇裂鼻畸形形成的重要原因之一。