Posterior Axis Research Articles

Wnt signaling establishes the microtubule polarity in neurons through regulation of Kinesin-13

Neuronal polarization is facilitated by the formation of axons with parallel arrays of plus-end-out and dendrites with the nonuniform orientation of microtubules. In C. elegans, the posterior lateral microtubule (PLM) neuron is bipolar with its two processes growing along the anterior-posterior axis under the guidance of Wnt signaling. Here we found that loss of the Kinesin-13 family microtubule-depolymerizing enzyme KLP-7 led to the ectopic extension of axon-like processes from the PLM cell body. Live imaging of the microtubules and axonal transport revealed mixed polarity of the microtubules in the short posterior process, which is dependent on both KLP-7 and the minus-end binding protein PTRN-1. KLP-7 is positively regulated in the posterior process by planar cell polarity components of Wnt involving rho-1/rock to induce mixed polarity of microtubules, whereas it is negatively regulated in the anterior process by the unc-73/ced-10 cascade to establish a uniform microtubule polarity. Our work elucidates how evolutionarily conserved Wnt signaling establishes the microtubule polarity in neurons through Kinesin-13.

A novel approach to 3D bone creation in minutes : 3D ultrasound.

AimsThe objective of this study is to assess the use of ultrasound (US) as a radiation-free imaging modality to reconstruct 3D anatomy of the knee for use in preoperative templating in knee arthroplasty.MethodsUsing an US system, which is fitted with an electromagnetic (EM) tracker that is integrated into the US probe, allows 3D tracking of the probe, femur, and tibia. The raw US radiofrequency (RF) signals are acquired and, using real-time signal processing, bone boundaries are extracted. Bone boundaries and the tracking information are fused in a 3D point cloud for the femur and tibia. Using a statistical shaping model, the patient-specific surface is reconstructed by optimizing bone geometry to match the point clouds. An accuracy analysis was conducted for 17 cadavers by comparing the 3D US models with those created using CT. US scans from 15 users were compared in order to examine the effect of operator variability on the output.ResultsThe results revealed that the US bone models were accurate compared with the CT models (root mean squared error (RM)S: femur, 1.07 mm (SD 0.15); tibia, 1.02 mm (SD 0.13). Additionally, femoral landmarking proved to be accurate (transepicondylar axis: 1.07° (SD 0.65°); posterior condylar axis: 0.73° (SD 0.41°); distal condylar axis: 0.96° (SD 0.89°); medial anteroposterior (AP): 1.22 mm (SD 0.69); lateral AP: 1.21 mm (SD 1.02)). Tibial landmarking errors were slightly higher (posterior slope axis: 1.92° (SD 1.31°); and tubercle axis: 1.91° (SD 1.24°)). For implant sizing, 90% of the femora and 60% of the tibiae were sized correctly, while the remainder were only one size different from the required implant size. No difference was observed between moderate and skilled users.ConclusionThe 3D US bone models were proven to be closely matched compared with CT and suitable for preoperative planning. The 3D US is radiation-free and offers numerous clinical opportunities for bone visualization rapidly during clinic visits, to enable preoperative planning with implant sizing. There is potential to extend its application to 3D dynamic ligament balancing, and intraoperative registration for use with robots and navigation systems.Cite this article: Bone Joint J 2021;103-B(6 Supple A):81–86.

Septins and a formin have distinct functions in anaphase chiral cortical rotation in the Caenorhabditis elegans zygote.

Many cells and tissues exhibit chirality that stems from the chirality of proteins and polymers. In the Caenorhabditis elegans zygote, actomyosin contractility drives chiral rotation of the entire cortex circumferentially around the division plane during anaphase. How contractility is translated to cell-scale chirality, and what dictates handedness, are unknown. Septins are candidate contributors to cell-scale chirality because they anchor and cross-link the actomyosin cytoskeleton. We report that septins are required for anaphase cortical rotation. In contrast, the formin CYK-1, which we found to be enriched in the posterior in early anaphase, is not required for cortical rotation but contributes to its chirality. Simultaneous loss of septin and CYK-1 function led to abnormal and often reversed cortical rotation. Our results suggest that anaphase contractility leads to chiral rotation by releasing torsional stress generated during formin-based polymerization, which is polarized along the cell anterior–posterior axis and which accumulates due to actomyosin network connectivity. Our findings shed light on the molecular and physical bases for cellular chirality in the C. elegans zygote. We also identify conditions in which chiral rotation fails but animals are developmentally viable, opening avenues for future work on the relationship between early embryonic cellular chirality and animal body plan.

Physical Laws Shape Up HOX Gene Collinearity.

Hox gene collinearity (HGC) is a multi-scalar property of many animal phyla particularly important in embryogenesis. It relates entities and events occurring in Hox clusters inside the chromosome DNA and in embryonic tissues. These two entities differ in linear size by more than four orders of magnitude. HGC is observed as spatial collinearity (SC), where the Hox genes are located in the order (Hox1, Hox2, Hox3 …) along the 3′ to 5′ direction of DNA in the genome and a corresponding sequence of ontogenetic units (E1, E2, E3, …) located along the Anterior—Posterior axis of the embryo. Expression of Hox1 occurs in E1, Hox2 in E2, Hox3 in E3, etc. Besides SC, a temporal collinearity (TC) has been also observed in many vertebrates. According to TC, first Hox1 is expressed in E1; later, Hox2 is expressed in E2, followed by Hox3 in E3, etc. Lately, doubt has been raised about whether TC really exists. A biophysical model (BM) was formulated and tested during the last 20 years. According to BM, physical forces are created which pull the Hox genes one after the other, driving them to a transcription factory domain where they are transcribed. The existing experimental data support this BM description. Symmetry is a physical–mathematical property of matter that was explored in depth by Noether who formulated a ground-breaking theory (NT) that applies to all sizes of matter. NT may be applied to biology in order to explain the origin of HGC in animals developing not only along the A/P axis, but also to animals with circular symmetry.

Lateralized Effect of Thalamic Deep Brain Stimulation Location on Verbal Abstraction.

Regionalized thalamic activity has been implicated in language function, and yet the effect of thalamic deep brain stimulation (DBS) on language-related clinical outcomes is underexplored. The objective of this study was to determine if the location of stimulation within the thalamus correlates with changes in language-related neuropsychological outcomes following DBS for essential tremor. Thirty patients with essential tremor underwent comprehensive neuropsychological evaluations before and after DBS surgery targeting the ventral intermediate nucleus of the thalamus. Changes in neuropsychological functions were evaluated. The relationships between language-related outcomes and stimulation location were assessed using both categorical and linear methods. Any significant results were further validated using linear discriminant analysis. Most neuropsychological functions remained unchanged at the group level. However, outcome on a measure of verbal abstraction was significantly dependent on stimulation location along the anterior-posterior axis within the left ventral lateral thalamus, with anterior stimulation associated with reduced verbal abstraction performance. This result was supported by linear discriminant analysis, which showed that stimulation locations with improved and reduced verbal abstraction function were best separated by a vector nearly parallel to the anterior-posterior axis. No stimulation location dependence was found for verbal abstraction outcome in the right thalamus or for outcomes of other language functions in either hemisphere. We demonstrate an effect of thalamic DBS on verbal abstraction as a function of left thalamic topography. This finding provides clinical evidence for the lateralization and regionalization of thalamic language function that may be relevant for understanding nonmotor effects of stimulation. © 2021 International Parkinson and Movement Disorder Society.

Robust integration of multiple single-cell RNA sequencing datasets using a single reference space.

In many biological applications of single-cell RNA sequencing (scRNA-seq), an integrated analysis of data from multiple batches or studies is necessary. Current methods typically achieve integration using shared cell types or covariance correlation between datasets, which can distort biological signals. Here we introduce an algorithm that uses the gene eigenvectors from a reference dataset to establish a global frame for integration. Using simulated and real datasets, we demonstrate that this approach, called Reference Principal Component Integration (RPCI), consistently outperforms other methods by multiple metrics, with clear advantages in preserving genuine cross-sample gene expression differences in matching cell types, such as those present in cells at distinct developmental stages or in perturbated versus control studies. Moreover, RPCI maintains this robust performance when multiple datasets are integrated. Finally, we applied RPCI to scRNA-seq data for mouse gut endoderm development and revealed temporal emergence of genetic programs helping establish the anterior-posterior axis in visceral endoderm.

Differential Spatiotemporal Expression of Type I and Type II Cadherins Associated With the Segmentation of the Central Nervous System and Formation of Brain Nuclei in the Developing Mouse.

Type I and type II classical cadherins comprise a family of cell adhesion molecules that regulate cell sorting and tissue separation by forming specific homo and heterophilic bonds. Factors that affect cadherin-mediated cell-cell adhesion include cadherin binding affinity and expression level. This study examines the expression pattern of type I cadherins (Cdh1, Cdh2, Cdh3, and Cdh4), type II cadherins (Cdh6, Cdh7, Cdh8, Cdh9, Cdh10, Cdh11, Cdh12, Cdh18, Cdh20, and Cdh24), and the atypical cadherin 13 (Cdh13) during distinct morphogenetic events in the developing mouse central nervous system from embryonic day 11.5 to postnatal day 56. Cadherin mRNA expression levels obtained from in situ hybridization experiments carried out at the Allen Institute for Brain Science (https://alleninstitute.org/) were retrieved from the Allen Developing Mouse Brain Atlas. Cdh2 is the most abundantly expressed type I cadherin throughout development, while Cdh1, Cdh3, and Cdh4 are expressed at low levels. Type II cadherins show a dynamic pattern of expression that varies between neuroanatomical structures and developmental ages. Atypical Cdh13 expression pattern correlates with Cdh2 in abundancy and localization. Analyses of cadherin-mediated relative adhesion estimated from their expression level and binding affinity show substantial differences in adhesive properties between regions of the neural tube associated with the segmentation along the anterior–posterior axis. Differences in relative adhesion were also observed between brain nuclei in the developing subpallium (basal ganglia), suggesting that differential cell adhesion contributes to the segregation of neuronal pools. In the adult cerebral cortex, type II cadherins Cdh6, Cdh8, Cdh10, and Cdh12 are abundant in intermediate layers, while Cdh11 shows a gradated expression from the deeper layer 6 to the superficial layer 1, and Cdh9, Cdh18, and Cdh24 are more abundant in the deeper layers. Person’s correlation analyses of cadherins mRNA expression patterns between areas and layers of the cerebral cortex and the nuclei of the subpallium show significant correlations between certain cortical areas and the basal ganglia. The study shows that differential cadherin expression and cadherin-mediated adhesion are associated with a wide range of morphogenetic events in the developing central nervous system including the organization of neurons into layers, the segregation of neurons into nuclei, and the formation of neuronal circuits.

Interactions between the WEE-1.3 kinase and the PAM-1 aminopeptidase in oocyte maturation and the early C. elegans embryo.

Puromycin-sensitive aminopeptidases are found across phyla and are known to regulate the cell-cycle and play a protective role in neurodegenerative disease. PAM-1 is a puromycin-sensitive aminopeptidase important for meiotic exit and polarity establishment in the one-cell Caenorhabditis elegans embryo. Despite conservation of this aminopeptidase, little is known about its targets during development. In order to identify novel interactors, we conducted a suppressor screen and isolated four suppressing mutations in three genes that partially rescued the maternal-effect lethality of pam-1 mutants. Suppressed strains show improved embryonic viability and polarization of the anterior–posterior axis. We identified a missense mutation in wee-1.3 in one of these suppressed strains. WEE-1.3 is an inhibitory kinase that regulates maturation promoting factor. Although the missense mutation suppressed polarity phenotypes in pam-1, it does so without restoring centrosome–cortical contact or altering the cortical actomyosin cytoskeleton. To see if PAM-1 and WEE-1.3 interact in other processes, we examined oocyte maturation. Although depletion of wee-1.3 causes sterility due to precocious oocyte maturation, this effect was lessened in pam-1 worms, suggesting that PAM-1 and WEE-1.3 interact in this process. Levels of WEE-1.3 were comparable between wild-type and pam-1 strains, suggesting that WEE-1.3 is not a direct target of the aminopeptidase. Thus, we have established an interaction between PAM-1 and WEE-1.3 in multiple developmental processes and have identified suppressors that are likely to further our understanding of the role of puromycin-sensitive aminopeptidases during development.

Reliability of Imageless Computer-Assisted Navigation for Femoral Rotational Alignment in Total Knee Arthroplasty.

Introduction:The aim of this study was to evaluate the reliability of the femoral component rotation on intra-operative data recorded in a computer-assisted navigation system (CAN-FRA) compared with the post-operative femoral component rotation observed on computed tomography (CT-FRA).Material and method:Computer-assisted total knee arthroplasty (TKA) or primary osteoarthritis of the knee was performed in 51 knees in 36 patients with a mean age of 69.51 years. All procedures were performed by a single surgeon using the same implant design. The intraclass correlation coefficient (ICC) was used to compare the intra-operative CAN-FRA with the post-operative CT-FRA. The angle between the anatomical epicondylar axis and the posterior condylar axis of the implant (CT-FRA) was measured at two separate timepoints by three observers who were blinded to the intra-operative CAN-FRA. Internal rotation was defined as rotation in the negative direction, while external rotation was defined as positive.Results:The mean intra-operative CAN-FRA was 0.1° ± 2.8° (range -5.0° to 5.5°). The mean post-operative CT-FRA was -1.3° ± 2.1° (range -4.6° to 4.4°). The mean difference between the CAN-FRA and the CT-FRA was -1.3° ± 2.2° (range -7.9° to 2.4°). The respective ICC values for the three observers were 0.92, 0.94, and 0.93, while the respective intra-observer coefficients were 0.91, 0.85, and 0.90. The ICC for the intra-operative CAN-FRA versus the post-operative CT-FRA was 0.71.Conclusion:This study shows that using a computer-assisted navigation system in TKA achieves reliable results and helps to achieve optimal positioning of the femoral component and rotation alignment correction.

Anatomic Considerations of Microvascular Free Tissue Transfer in Endoscopic Endonasal Skull Base Surgery

Objective Though microvascular free tissue transfer is well established for open skull base reconstruction, normative data regarding flap design and inset after endoscopic endonasal skull base surgery (ESBS) is lacking. We aim to describe anatomical considerations of endoscopic endonasal inset of free tissue transfer of transclival (TC) and anterior cranial base resection (ACBR) defects. Design and Setting Radial forearm free tissue transfer (RFFTT) model. Participants Six cadaveric specimens. Main Outcome Measures Pedicle orientation, pedicle length, and recipient vessel intraluminal diameter. Results TC and ACBR defects averaged 17.2 and 11.7 cm 2 , respectively. Anterior and lateral maxillotomies and endoscopic medial maxillectomies were prepared as corridors for flap and pedicle passage. Premasseteric space tunnels were created for pedicle tunneling to recipient facial vessels. For TC defects, the RFFTT pedicle was oriented cranially with the flap placed against the clival defect (mean pedicle length 13.1 ± 0.6 cm). For ACBR defects, the RFFTT pedicle was examined in three orientations with respect to anterior-posterior axis of the RFFTT: anteriorly, posteriorly, and laterally. Lateral orientation offered the shortest average pedicle length required for anastomosis in the neck (11.6 ± 1.29 cm), followed by posterior (13.4 ± 0.7cm) and anterior orientations (14.4 ± 1.1cm) ( p < 0.00001, analysis of variance). Conclusions In ACBR reconstruction using RFFTT, our data suggests lateral pedicle orientation shortens the length required to safely anastomose facial vessels and protects the frontal sinus outflow anteriorly while limiting pedicle exposure through a maxillary corridor within the nasal cavity. With greater understanding of anatomical factors related to successful preoperative flap planning, free tissue transfer may be added to the ESBS reconstruction ladder.

The Collagens DPY-17 and SQT-3 Direct Anterior-Posterior Migration of the Q Neuroblasts in C. elegans.

Cell adhesion molecules and their extracellular ligands control morphogenetic events such as directed cell migration. The migration of neuroblasts and neural crest cells establishes the structure of the central and peripheral nervous systems. In C. elegans, the bilateral Q neuroblasts and their descendants undergo long-range migrations with left/right asymmetry. QR and its descendants on the right migrate anteriorly, and QL and its descendants on the left migrate posteriorly, despite identical patterns of cell division, cell death, and neuronal generation. The initial direction of protrusion of the Q cells relies on the left/right asymmetric functions of the transmembrane receptors UNC-40/DCC and PTP-3/LAR in the Q cells. Here, we show that Q cell left/right asymmetry of migration is independent of the GPA-16/Gα pathway which regulates other left/right asymmetries, including nervous system L/R asymmetry. No extracellular cue has been identified that guides initial Q anterior versus posterior migrations. We show that collagens DPY-17 and SQT-3 control initial Q direction of protrusion. Genetic interactions with UNC-40/DCC and PTP-3/LAR suggest that DPY-17 and SQT-3 drive posterior migration and might act with both receptors or in a parallel pathway. Analysis of mutants in other collagens and extracellular matrix components indicated that general perturbation of collagens and the extracellular matrix (ECM) did not result in directional defects, and that the effect of DPY-17 and SQT-3 on Q direction is specific. DPY-17 and SQT-3 are components of the cuticle, but a role in the basement membrane cannot be excluded. Possibly, DPY-17 and SQT-3 are part of a pattern in the cuticle and/or basement membrane that is oriented to the anterior–posterior axis of the animal and that is deciphered by the Q cells in a left–right asymmetric fashion. Alternatively, DPY-17 and SQT-3 might be involved in the production or stabilization of a guidance cue that directs Q migrations. In any case, these results describe a novel role for the DPY-17 and SQT-3 collagens in directing posterior Q neuroblast migration.

Medio-Lateral and Flexion-Extension Gap Imbalances in Mechanically Aligned Total Knee Arthroplasty Using Measured Resection Technique in Korean Patients: 3D Simulation.

Background: It is well known that the measured resection (MR) technique in mechanically aligned (MA) total knee arthroplasty (TKA) generates significant gap imbalances, but little is known about whether this applies to the knees of Asian patients. The aim of this study was to evaluate the medio-lateral and flexion-extension gap imbalances and to find the most optimal posterior femoral condyle resection method for operating on the knees of Asian patients. Methods: In total, 738 magnetic resonance imaging (MRI) scans of consecutive patients who underwent TKA were obtained. Four posterior femoral condylar resection methods were used: alignment by the surgical transepicondylar axis (TEA), Whiteside’s line (WSL), 3° external rotation to the posterior condylar axis (PCA), and flexion-extension axis (FEA). Results: For the medial compartments, there were significant differences between the flexion and extension gaps in the varus knee group in all four methods, but there were no differences between the flexion and extension gaps in the valgus knee group. For the lateral compartment, all the methods showed significant differences except for WSL of the valgus knee group and FEA of the varus knee group. Conclusions: In Asian patients, the use of the MA MR technique inevitably leads to medio-lateral or flexion-extension imbalances. Therefore, surgeons should consider which methods can minimize imbalances and choose the best method within the technically possible range.

Organization of Afferents along the Anterior–posterior and Medial–lateral Axes of the Rat Orbitofrontal Cortex

The orbitofrontal cortex (OFC) has been anatomically divided into a number of subregions along its medial–lateral axis, which behavioral research suggests have distinct functions. Recently, evidence has emerged suggesting functional diversity is also present along the anterior–posterior axis of the rodent OFC. However, the patterns of anatomical connections that underlie these differences have not been well characterized. Here, we use the retrograde tracer cholera toxin subunit B (CTB) to simultaneously label the projections into the anterior lateral (ALO), posterior lateral (PLO), and posterior ventral (PVO) portions of the rat OFC. Our methodological approach allowed us to simultaneously compare the density and input patterns into these OFC subdivisions. We observed distinct and topographically organized projection patterns into ALO, PLO, and PVO from the mediodorsal and the submedius nuclei of the thalamus. We also observed different levels of connectivity strength into these OFC subdivisions from the amygdala, motor cortex, sensory cortices and medial prefrontal cortical structures, including medial OFC, infralimbic and prelimbic cortices. Interestingly, while labelling in some of these input regions revealed only a gradient in connectivity strength, other regions seem to project almost exclusively to specific OFC subdivisions. Moreover, differences in input patterns between ALO and PLO were as pronounced as those between PLO and PVO. Together, our results support the existence of distinct anatomical circuits within lateral OFC along its anterior–posterior axis.

A conserved role for arrow in posterior axis patterning across Arthropoda

Segmentation is a key characteristic of Arthropoda that is linked to the evolutionary success of this lineage. It has previously been shown in both vertebrates and short germ insects that posterior segmentation requires canonical Wnt (cWnt) signaling, which maintains the expression of Caudal and the posterior growth zone; disruption of cWnt signaling incurs posterior truncations in these lineages due to the loss of the tail bud. However, comparable datasets for Wnt signaling are limited outside of holometabolous insects, due to incomparable phenotypic spectra and inefficacy of gene misexpression methods in certain model species. We applied RNA interference (RNAi) against the Wnt co-receptor arrow (arr), a key member of the cWnt signaling pathway in holometabolous insects and vertebrates, to examine posterior axis elongation of the cobweb spider Parasteatoda tepidariorum (short germ embryogenesis; one Wnt8 homolog), the cricket Gryllus bimaculatus (intermediate germ; one Wnt8 homolog), and the milkweed bug Oncopeltus fasciatus (short germ; two Wnt8 homologs). Knockdown of arr in insects resulted in posterior truncations affecting the gnathos through the abdomen in O. fasciatus, whereas posterior truncations only affected the T3 segment through the abdomen in G. bimaculatus. Spider embryos with disrupted arr expression exhibited defects along the entire axis, including segmentation defects throughout the germband. RNA-Seq-based differential gene expression analysis of severe Ptep-arr loss-of-function phenotypes at two developmental stages was used to confirm that knockdown of Ptep-arr results in systemic disruption of the Wnt pathway. Intriguingly, we found that knockdown of arr did not abrogate Wnt8 expression in any of the three species, with cad expression additionally retained in severe loss-of-function phenotypes in the cricket and the spider. Together with data from a holometabolous insect, our results suggest that cWnt signaling is not required for maintenance of Wnt8 expression across Arthropoda. These outcomes underscore the diagnostic power of differential gene expression analyses in characterizing catastrophic phenotypes in emerging model species.

Total knee replacement wear during simulated gait with mechanical and anatomic alignments.

Total knee replacements (TKR) have historically been implanted perpendicular to the mechanical axis of the knee joint, with a commensurate external rotation of the femur in flexion relative to the posterior condylar axis (PCA). Although this mechanical alignment (MA) method has typically offered good long-term survivorship of implants, it may result in alignment of the implant that departs significantly from the native Joint Line (JL) in extension and flexion for a considerable portion of the patient population. There is a growing interest with surgeons to implant TKR components more closely aligned to the natural JL (Anatomic Alignment-AA) of the patient's knee joint to reduce the need for soft tissue releases during surgery, potentially improving knee function and patient satisfaction. Using a previously-validated finite element model of the lower extremity, implant- and alignment-specific loading conditions were developed and applied in a wear experiment via a six-degree-of-freedom joint simulator. MA was defined as 0° Joint Line (JL), 0° varus hip-knee-ankle (HKA) angle, and 3° external femoral rotation. AA was defined as 5° varus JL, 3° varus HKA, and 0° femoral rotation. The experiment returned wear rates of 3.76 ± 0.51 mg/million cycles (Mcyc) and 2.59 ± 2.11 mg/Mcyc for ATTUNE® cruciate-retaining (CR) fixed bearing (FB) in MA and AA, respectively. For ATTUNE posterior-stabilized (PS) FB in AA, the wear rate was 0.97 ± 1.11 mg/Mcyc. For ATTUNE CR rotating platform (RP), the wear rates were 0.23 ± 0.19 mg/Mcyc, 0.48 ± 1.02 mg/Mcyc in MA and AA respectively. Using a two-way ANOVA, it was determined that there was no significantly difference in the wear rates between AA and MA (p = 0.144) nor the wear rate of ATTUNE PS FB in AA significantly different from either ATTUNE CR FB or ATTUNE CR RP.

Dissecting human embryonic skeletal stem cell ontogeny by single-cell transcriptomic and functional analyses

Human skeletal stem cells (SSCs) have been discovered in fetal and adult long bones. However, the spatiotemporal ontogeny of human embryonic SSCs during early skeletogenesis remains elusive. Here we map the transcriptional landscape of human limb buds and embryonic long bones at single-cell resolution to address this fundamental question. We found remarkable heterogeneity within human limb bud mesenchyme and epithelium, and aligned them along the proximal–distal and anterior–posterior axes using known marker genes. Osteo-chondrogenic progenitors first appeared in the core limb bud mesenchyme, which give rise to multiple populations of stem/progenitor cells in embryonic long bones undergoing endochondral ossification. Importantly, a perichondrial embryonic skeletal stem/progenitor cell (eSSPC) subset was identified, which could self-renew and generate the osteochondral lineage cells, but not adipocytes or hematopoietic stroma. eSSPCs are marked by the adhesion molecule CADM1 and highly enriched with FOXP1/2 transcriptional network. Interestingly, neural crest-derived cells with similar phenotypic markers and transcriptional networks were also found in the sagittal suture of human embryonic calvaria. Taken together, this study revealed the cellular heterogeneity and lineage hierarchy during human embryonic skeletogenesis, and identified distinct skeletal stem/progenitor cells that orchestrate endochondral and intramembranous ossification.

Sulcal Morphology in Cingulate Cortex is Associated with Voluntary Oro-Facial Motor Control and Gestural Communication in Chimpanzees (Pan troglodytes).

Individual differences in sulcal variation within the anterior and mid-cingulate cortex of the human brain, particularly the presence or absence of a paracingulate sulcus (PCGS), are associated with various motor and cognitive processes. Recently, it has been reported that chimpanzees possess a PCGS, previously thought to be a unique feature of the human brain. Here, we examined whether individual variation in the presence or absence of a PCGS as well as the variability in the intralimbic sulcus (ILS) are associated with oro-facial motor control, handedness for manual gestures, and sex in a sample of MRI scans obtained in 225 chimpanzees. Additionally, we quantified the depth of the cingulate sulcus (CGS) along the anterior-posterior axis and tested for association with oro-facial motor control, handedness, and sex. Chimpanzees with better oro-facial motor control were more likely to have a PCGS, particularly in the left hemisphere compared to those with poorer control. Male chimpanzees with better oro-facial motor control showed increased leftward asymmetries in the depth of the anterior CGS, whereas female chimpanzees showed the opposite pattern. Significantly, more chimpanzees had an ILS in the left compared to the right hemisphere, but variability in this fold was not associated with sex, handedness, or oro-facial motor control. Finally, significant population-level leftward asymmetries were found in the anterior portion of the CGS, whereas significant rightward biases were evident in the posterior regions. The collective results suggest that the emergence of a PCGS and enhanced gyrification within the anterior and mid-cingulate gyrus may have directly or indirectly evolved in response to selection for increasing oro-facial motor control in primates.

Three Degrees External to the Posterior Condylar Axis Has Little Relevance in Femoral Component Rotation: A Computed Tomography-Based Total Knee Arthroplasty Simulation Study

BackgroundFemoral component rotation in total knee arthroplasty (TKA) has a significant impact on balance and patellofemoral kinematics. However, normal anatomic relationships between rotational axes are poorly understood. As such, we sought to characterize anatomic femoral rotational axes in patients undergoing primary TKA. MethodsWe identified 100 patients who underwent a primary TKA with a preoperative computed tomography scan. The angles between the surgical epicondylar axis (SEA) and the anterior-posterior (AP) axis to the posterior condylar axis (PCA) were measured independently by a musculoskeletal fellowship-trained radiologist and a fellowship-trained arthroplasty surgeon. We simulated an ideal TKA in which the femoral component was placed exactly 3° external to the PCA and measured resulting rotation. ResultsThe SEA was on average 1.5° externally rotated to the PCA (range 3.1° internal to 7.0° external). The AP axis was on average 4.5° externally rotated to the PCA (range 2.3° internal to 10.3° external). The AP axis was a mean 2.7° externally rotated to the SEA (range 6.3° internal to 10.3° external). Routinely setting femoral rotation 3° external to the PCA would result in only 51 (51%) TKAs within ±2° of the SEA and 23 (23%) femoral components internally rotated relative to the SEA. ConclusionNormal anatomic rotational axes of arthritic knees are highly variable, with a 10° range in the SEA and 16° range in the AP axis. Routinely setting femoral rotation 3° external to the PCA will yield significant error in aligning the femoral component with either the SEA or AP axis.

Effects of orthokeratology lenses and frame glasses on anisometropia in primary and middle school students with low myopia in one eye

Objective To investigate the effects of orthokeratology lenses and frame glasses on anisometropia in children with low myopia in one eye. Methods Between January 2017 and January 2018, 120 children of primary and secondary school age with myopic anisometropia low myopia in one eye presenting to the Second People’s Hospital of Yunnan Province were selected as research objects, with average refractive error of (–1.00, –2.50) D in one eye and (–0.50, 0.50) D in another eye. Participants were divided into an experimental group and a control group (60 cases per group), according to a random number grouping method. The control group were given frame glasses, while the experimental group were given orthokeratology lenses. A prospective study was conducted to compare and analyze the lengths of the posterior eye axis (AL) and spherical equivalent (SE), measured at different time intervals between the two groups. Results There were some initial differences in AL and SE between the two groups before the experiment began; however, this difference was not statistically significant ( P >0.05). After 12 months, participants myopic eyes given the orthokeratology lenses had shorter AL [(24.91±0.11) mm] compared to the control group [(25.02±0.09) mm], participants health eyes had longer AL [(24.58±0.24) mm] compared to the control group [(24.20±0.13) mm]. One month after the subjects stopped wearing plastic mirrors, participants myopic eyes had higher SE [(–2.22±0.78) D] compared to the control group [(–2.64土 0.21) D], and had lower that in the control group [(–0.96±0.84) (–0.37±0.54) D] ( t = 4.02, –4.58, P 0.05);配戴12个月后, 试验组戴镜眼AL[(24.91±0.11)mm]较对照组 [(25.02±0.09)mm]短, 对侧眼AL [(24.58±0.24) mm]较对照组[(24.20±0.13) mm]长。停戴塑形镜1月后, 试验组戴镜眼 SE[(–2.22±0.78)D]较对照组[(–2.64±0.21)D]高, 对侧眼 SE [(–0.96±0.84)D]较对照组[(–0.37±0.54) D]低, 差异均有 统计学意义（ t 值分别为4.02, –4.58, P 值均<0.05)。 结论 与佩戴框架镜相比, 配戴角膜塑形镜可有效抑制单眼近视患儿 患眼AL延长、控制患眼近视进展, 促进对侧健眼眼轴延长及屈光度增加, 降低屈光参差值, 在一定程度上解决双眼视轴发 育不平衡的问题, 促进双眼协调发展。

The posterior cortical axis as an alternative reference for femoral component placement in total knee arthroplasty

BackgroundAlthough several reference axes have been established for determining femoral rotational alignment during total knee arthroplasty (TKA), the most accurate axis is undetermined. This study determines the relationship between the posterior cortical axis (PCA) and the trochlear anterior line (TAL) of the femur in relation to the epicondylar axis.MethodsA total of 341 patients who underwent TKA for osteoarthritis were enrolled. Patients who had undergone previous bony surgery or replacement that might have changed the femoral geometry were excluded. Finally, 336 patients (200 females and 136 males) were included in the study. The angles between the transepicondylar axis (TEA) and TAL and TEA and the femoral PCA (FPCA) were evaluated. We also assessed whether there was any significant differences in variance and gender in these two angles. Student’s t tests were used to determine the significance of coronal alignment and any gender-based differences. The variances between the TAL/TEA and FPCA/TEA angles were compared using F tests.ResultsThe FPCA was externally rotated by 2.6° ± 3.6°, and the trochlear anterior line was internally rotated by 5.2° ± 5.5°, relative to the TEA. Gender-based differences were observed in the comparisons between anatomical references and TEA.ConclusionsThe FPCA is a more conservative landmark than the TAL for intraoperative or postoperative approximation of the TEA. When conventional reference axes, such as the posterior condylar axis and the anteroposterior axis, are inaccurate, surgeons can refer to this alternative reference. These findings demonstrate that the FPCA may be useful for determining the rotational alignment of the femoral component before and during TKA.