KPNB1 mediates PER/CRY nuclear translocation and circadian clock function.

Regulated nuclear translocation of the PER/CRY repressor complex is critical for negative feedback regulation of the circadian clock of mammals. However, the precise molecular mechanism is not fully understood. Here, we report that KPNB1, an importin ß component of the ncRNA repressor of nuclear factor of activated T cells (NRON) ribonucleoprotein complex, mediates nuclear translocation and repressor function of the PER/CRY complex. RNAi depletion of KPNB1 traps the PER/CRY complex in the cytoplasm by blocking nuclear entry of PER proteins in human cells. KPNB1 interacts mainly with PER proteins and directs PER/CRY nuclear transport in a circadian fashion. Interestingly, KPNB1 regulates the PER/CRY nuclear entry and repressor function, independently of importin α, its classical partner. Moreover, inducible inhibition of the conserved Drosophila importin ß in lateral neurons abolishes behavioral rhythms in flies. Collectively, these data show that KPNB1 is required for timely nuclear import of PER/CRY in the negative feedback regulation of the circadian clock.

Delayed Vertebral Artery Dissection after Posterior Cervical Fusion with Traumatic Cervical Instability: A Case Report.

Vascular injury presented immediately after the penetration, but delayed onset of vascular symptom caused by an embolism or vessel dissection after cervical fusion or traumatic event is extremely rare. We present a case of a 56-year-old woman who underwent an operation for cervical fusion for type II Odontoid process fracture. She presented symptoms of seizure with hemiparesis in 6 days after the operation. Multifocal acute infarction due to an embolism from the left VA (V3 segment) dissection was observed without a definite screw breach the transverse foramen. We hereby reported the instructive case report of delayed onset of vertebral artery dissection after posterior cervical fusion with type II odontoid process fracture patient. When a cervical operation performed in the cervical trauma patient, even if no apparent VA injury occurs before and during the operation, the surgeon must take caution not to risk cerebral infarction because of the delayed VA dissection.

Drosophila TIM binds importin α1, and acts as an adapter to transport PER to the nucleus.

Regulated nuclear entry of clock proteins is a conserved feature of eukaryotic circadian clocks and serves to separate the phase of mRNA activation from mRNA repression in the molecular feedback loop. In Drosophila, nuclear entry of the clock proteins, PERIOD (PER) and TIMELESS (TIM), is tightly controlled, and impairments of this process produce profound behavioral phenotypes. We report here that nuclear entry of PER-TIM in clock cells, and consequently behavioral rhythms, require a specific member of a classic nuclear import pathway, Importin α1 (IMPα1). In addition to IMPα1, rhythmic behavior and nuclear expression of PER-TIM require a specific nuclear pore protein, Nup153, and Ran-GTPase. IMPα1 can also drive rapid and efficient nuclear expression of TIM and PER in cultured cells, although the effect on PER is mediated by TIM. Mapping of interaction domains between IMPα1 and TIM/PER suggests that TIM is the primary cargo for the importin machinery. This is supported by attenuated interaction of IMPα1 with TIM carrying a mutation previously shown to prevent nuclear entry of TIM and PER. TIM is detected at the nuclear envelope, and computational modeling suggests that it contains HEAT-ARM repeats typically found in karyopherins, consistent with its role as a co-transporter for PER. These findings suggest that although PER is the major timekeeper of the clock, TIM is the primary target of nuclear import mechanisms. Thus, the circadian clock uses specific components of the importin pathway with a novel twist in that TIM serves a karyopherin-like role for PER.

Surface Landmarks do not Correspond to Exact Levels of the Cervical Spine: References According to the Sex, Age and Height.

OBJECTIVE: A general orientation along the cervical spine could be estimated by external landmarks, and it was useful, quick and less exposable to radiation, but, sometimes it gave reference confusion of target cervical level. The authors reviewed the corresponding between the neck external landmarks and cervical levels. METHODS: Totally 1,031 cervical lateral radiographs of different patients were reviewed in single university hospital. Its compositions were 534 of males and 497 females; 86 of second decades (10-19 years-old), 169 of third decades, 159 of fourth decades, 209 of fifth decades, 275 of sixth decades, and 133 of more than seventh decades (>60 years-old). Reference external landmarks (mandible, hyoid bone, thyroid cartilage, and cricothyroid membrane) with compounding factors were reviewed. RESULTS: The reference levels of cervical landmarks were C2.13 with mandible angle, C3.54 with hyoid bone, C5.12 with thyroid cartilage, and C6.01 with cricothyroid membrane. The reference levels of cervical landmarks were differently observed by sex, age, and somatometric measurement (height) accordingly mandible angle from C1 to C3, hyoid bone from disc level of C2 and C3 to C5, thyroid cartilage from disc level of C3 and C4 to C7, and cricothyroid membrane from C4 to disc level of C7 and T1. CONCLUSION: Surface landmarks only provide general reference points, but not correspond to exact levels of the cervical spine. Intraoperative fluoroscopy ensures a more precise placement to the targeted cervical level.