Chromosome congression is promoted by CENP-Q- and CENP-E-dependent pathways

A key step of mitosis is the congression of chromosomes to the spindle equator. Congression is driven by at least two distinct mechanisms: (1) kinetochores slide along the microtubule lattice using the plus-end directed CENP-E motor, and (2) kinetochores biorientating near the pole move to the equator through microtubule depolymerisation-coupled pulling. Here, we show that CENP-Q - a subunit of the CENP-O complex (comprising CENP-O, CENP-P, CENP-Q and CENP-U) that targets polo-like kinase (Plk1) to kinetochores - is also required for the recruitment of CENP-E to kinetochores. We further reveal a CENP-E recruitment-independent role for CENP-Q in depolymerisation-coupled pulling. Both of these functions are abolished by a single point mutation in CENP-Q (S50A) - a residue that is phosphorylated in vivo. Importantly, the S50A mutant does not affect the loading of Plk1 onto kinetochores and leaves the CENP-O complex intact. Thus, the functions of CENP-Q in CENP-E loading and depolymerisation-coupled pulling are independent from its role in Plk1 recruitment and CENP-O complex stabilisation. Taken together, our data provide evidence that phosphoregulation of CENP-Q plays a central function in coordinating chromosome congression mechanisms

Self-Organized Criticality in Developing Neuronal Networks

Recently evidence has accumulated that many neural networks exhibit self-organized criticality. In this state, activity is similar across temporal scales and this is beneficial with respect to information flow. If subcritical, activity can die out, if supercritical epileptiform patterns may occur. Little is known about how developing networks will reach and stabilize criticality. Here we monitor the development between 13 and 95 days in vitro (DIV) of cortical cell cultures (n = 20) and find four different phases, related to their morphological maturation: An initial low-activity state (≈19 DIV) is followed by a supercritical (≈20 DIV) and then a subcritical one (≈36 DIV) until the network finally reaches stable criticality (≈58 DIV). Using network modeling and mathematical analysis we describe the dynamics of the emergent connectivity in such developing systems. Based on physiological observations, the synaptic development in the model is determined by the drive of the neurons to adjust their connectivity for reaching on average firing rate homeostasis. We predict a specific time course for the maturation of inhibition, with strong onset and delayed pruning, and that total synaptic connectivity should be strongly linked to the relative levels of excitation and inhibition. These results demonstrate that the interplay between activity and connectivity guides developing networks into criticality suggesting that this may be a generic and stable state of many networks in vivo and in vitro

The nucleoporin ALADIN regulates Aurora A localization to ensure robust mitotic spindle formation

The formation of the mitotic spindle is a complex process that requires massive cellular reorganization. Regulation by mitotic kinases controls this entire process. One of these mitotic controllers is Aurora A kinase, which is itself highly regulated. In this study, we show that the nuclear pore protein ALADIN is a novel spatial regulator of Aurora A. Without ALADIN, Aurora A spreads from centrosomes onto spindle microtubules, which affects the distribution of a subset of microtubule regulators and slows spindle assembly and chromosome alignment. ALADIN interacts with inactive Aurora A and is recruited to the spindle pole after Aurora A inhibition. Of interest, mutations in ALADIN cause triple A syndrome. We find that some of the mitotic phenotypes that we observe after ALADIN depletion also occur in cells from triple A syndrome patients, which raises the possibility that mitotic errors may underlie part of the etiology of this syndrome

Retro-trochanteric sciatica-like pain: current concept

The aim of this manuscript is to review the current knowledge in terms of retro-trochanteric pain syndrome, make recommendations for diagnosis and differential diagnosis and offer suggestions for treatment options. The terminology in the literature is confusing and these symptoms can be referred to as ‘greater trochanteric pain syndrome’, ‘trochanteric bursitis’ and ‘trochanteritis’, among other denominations. The authors focus on a special type of sciatica, i.e. retro-trochanteric pain radiating down to the lower extremity. The impact of different radiographic assessments is discussed. The authors recommend excluding pathology in the spine and pelvic area before following their suggested treatment algorithm for sciatica-like retro-trochanteric pain. Level of evidence II

CENP-32 is required to maintain centrosomal dominance in bipolar spindle assembly

Centrosomes nucleate spindle formation, direct spindle pole positioning, and are important for proper chromosome segregation during mitosis in most animal cells. We previously reported that centromere protein 32 (CENP-32) is required for centrosome association with spindle poles during metaphase. In this study, we show that CENP-32 depletion seems to release centrosomes from bipolar spindles whose assembly they had previously initiated. Remarkably, the resulting anastral spindles function normally, aligning the chromosomes to a metaphase plate and entering anaphase without detectable interference from the free centrosomes, which appear to behave as free asters in these cells. The free asters, which contain reduced but significant levels of CDK5RAP2, show weak interactions with spindle microtubules but do not seem to make productive attachments to kinetochores. Thus CENP-32 appears to be required for centrosomes to integrate into a fully functional spindle that not only nucleates astral microtubules, but also is able to nucleate and bind to kinetochore and central spindle microtubules. Additional data suggest that NuMA tethers microtubules at the anastral spindle poles and that augmin is required for centrosome detachment after CENP-32 depletion, possibly due to an imbalance of forces within the spindle

Changes in Cerebral Oxygenation during Transfusion Therapy

This study assesses the effects of transfusion of autologous or allogeneic blood on cerebral and tissue oxygenation during spinal surgery. Packed red blood cell transfusions are indicated to improve oxygen delivery to tissues. There are limited data demonstrating changes in tissue oxygenation with blood administration. Tissue (deltoid) and cerebral oxygenation were monitored using near-infrared spectroscopy during spinal surgery in patients. As indicated, cell saver or allogeneic blood was administered. Tissue and cerebral oxygenation were recorded before and after transfusion. The study enrolled 50 patients, 33 of whom (17 males and 16 females) received allogeneic blood (n = 8) or autologous blood (n = 25). Patients ranged in age from 9 to 19 years (14.0 ± 2.3 years) and in weight from 16.8 to 122.7 kg (54.6 ± 25.7 kg). Tissue oxygenation increased from 83 ± 9 (pretransfusion) to 86 ± 7 at the end of transfusion (p = .002) and remained at the same level (86 ± 7) in the post-transfusion period. Cerebral oxygenation increased from 76 ± 8 (pretransfusion) to 84 ± 8 at the end of transfusion (p < .001) and remained at 84 ± 8 in the post-transfusion period. Changes in tissue and cerebral oxygenation were similar between cell saver and allogeneic blood and between starting hemoglobin value <8 gm/dL and starting hemoglobin ≥8 gm/dL. In conclusion, although both cerebral and tissue oxygenation increased during the administration of either allogeneic or autologous blood, the clinical impact was likely limited given the high initial tissue and cerebral oxygenation values. No differences were noted between autologous (cell saver) and allogeneic blood or based on the starting hemoglobin value

Spinal anesthesia instead of general anesthesia for infants undergoing tendon Achilles lengthening

Spinal anesthesia (SA) has been used relatively sparingly in the pediatric population, as it is typically reserved for patients in whom the perceived risk of general anesthesia is high due to comorbid conditions. Recently, concern has been expressed regarding the potential long-term neurocognitive effects of general anesthesia during the early stages of life. In view of this, our center has developed a program in which SA may be used as the sole agent for applicable surgical procedures. While this approach in children is commonly used for urologic or abdominal surgical procedures, there have been a limited number of reports of its use for orthopedic procedures in this population. We present the use of SA for 6 infants undergoing tendon Achilles lengthening, review the use of SA in orthopedic surgery, describe our protocols and dosing regimens, and discuss the potential adverse effects related to this technique

Spinal anesthesia instead of general anesthesia for infants undergoing tendon Achilles lengthening.

Spinal anesthesia (SA) has been used relatively sparingly in the pediatric population, as it is typically reserved for patients in whom the perceived risk of general anesthesia is high due to comorbid conditions. Recently, concern has been expressed regarding the potential long-term neurocognitive effects of general anesthesia during the early stages of life. In view of this, our center has developed a program in which SA may be used as the sole agent for applicable surgical procedures. While this approach in children is commonly used for urologic or abdominal surgical procedures, there have been a limited number of reports of its use for orthopedic procedures in this population. We present the use of SA for 6 infants undergoing tendon Achilles lengthening, review the use of SA in orthopedic surgery, describe our protocols and dosing regimens, and discuss the potential adverse effects related to this technique