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PLoS Computational Biology Apr 2020In multicellular organisms, the timing and placement of gene expression in a developing tissue assigns the fate of each cell in the embryo in order for a uniform field...
In multicellular organisms, the timing and placement of gene expression in a developing tissue assigns the fate of each cell in the embryo in order for a uniform field of cells to differentiate into a reproducible pattern of organs and tissues. This positional information is often achieved through the action of spatial gradients of morphogens. Spatial patterns of gene expression are paradoxically robust to variations in morphogen dosage, given that, by definition, gene expression must be sensitive to morphogen concentration. In this work we investigate the robustness of the Dorsal/NF-κB signaling module with respect to perturbations to the dosage of maternally-expressed dorsal mRNA. The Dorsal morphogen gradient patterns the dorsal-ventral axis of the early Drosophila embryo, and we found that an empirical description of the Dorsal gradient is highly sensitive to maternal dorsal dosage. In contrast, we found experimentally that gene expression patterns are highly robust. Although the components of this signaling module have been characterized in detail, how their function is integrated to produce robust gene expression patterns to variations in the dorsal maternal dosage is still unclear. Therefore, we analyzed a mechanistic model of the Dorsal signaling module and found that Cactus, a cytoplasmic inhibitor for Dorsal, must be present in the nucleus for the system to be robust. Furthermore, active Toll, the receptor that dissociates Cactus from Dorsal, must be saturated. Finally, the vast majority of robust descriptions of the system require facilitated diffusion of Dorsal by Cactus. Each of these three recently-discovered mechanisms of the Dorsal module are critical for robustness. These mechanisms synergistically contribute to changing the amplitude and shape of the active Dorsal gradient, which is required for robust gene expression. Our work highlights the need for quantitative understanding of biophysical mechanisms of morphogen gradients in order to understand emergent phenotypes, such as robustness.
Topics: Animals; Body Patterning; Cell Nucleus; Cytoplasm; DNA-Binding Proteins; Drosophila; Drosophila Proteins; Embryo, Nonmammalian; Gene Expression Regulation, Developmental; Morphogenesis; NF-kappa B; Nuclear Proteins; Phosphoproteins; Signal Transduction; Transcription Factors
PubMed: 32251432
DOI: 10.1371/journal.pcbi.1007750 -
Journal of Thoracic Disease Oct 2022Segmentectomy is increasingly performed as a surgical technique. Traditional anterior axillary line and mid-axillary line video-assisted thoracoscopic surgery (VATS)...
Dorsal incision shows more efficacy and safety to traditional incision in single-portal video-assisted thoracoscopic surgery segmentectomy of LS9+10: a non-randomized prospective clinical trial.
BACKGROUND
Segmentectomy is increasingly performed as a surgical technique. Traditional anterior axillary line and mid-axillary line video-assisted thoracoscopic surgery (VATS) incision meets difficulties when dealing with left segment 9+10 (LS9+10), as the distance and angle of view make it uneasy to expose the trachea, blood vessels and intersegment plane. As an alternative, dorsal incision may be advantageous as which faces the key structures of LS9+10, may facilitate the management of trachea and blood vessels of LS9+10, but there was no clinical proof reported ever. This study is targeted to compare the efficacy and safety of these two incisions in segmentectomy of LS9+10.
METHODS
The dorsal incision is made behind the posterior axillary line, 8th intercostal space. Patients with ground glass opacity (GGO) which solid ingredients is less than 25%, locates at LS9+10, and segmentectomy of LS9+10 could ensure the cut edge were enrolled in the study and were allocated to the traditional incision group or dorsal incision group based on the parity of hospital number. Efficacy outcomes such as the duration of surgery and safety outcomes including postoperative air-leakage duration, length of hospital stay, amount of bleeding and pain score were recorded. The Independent-samples test and Mann-Whitey U test were applied in data analysis.
RESULTS
A total of 68 patients were enrolled and allocated into the traditional incision group and dorsal incision group. In the traditional incision group, the average surgery time was 71.03±6.87 min (median 71.5 min), while that in the dorsal incision group was an average of 62.72±6.24 min (median 61.0 min, P=0.001). The postoperative duration of air-leakage was 2.16±1.63 and 1.36±1.33 days for traditional incision group and dorsal incision group (P=0.030), respectively. The traditional incision group had a greater length of postoperative hospital stay (3.69±1.36 days) than the dorsal incision group (3.08±1.03 days, P=0.041), when amount of bleeding and pain score showed no differences between these two groups. Data suggested a statistically significant advantage for the dorsal incision procedure.
CONCLUSIONS
Dorsal incision can facilitate the segmentectomy of LS9+10, and significantly reduce the surgery time, postoperative duration of air-leakage and length of hospital stay.
PubMed: 36389335
DOI: 10.21037/jtd-22-1202 -
Journal of Orthopaedic Surgery and... Nov 2021The first dorsal metacarpal artery flap, including dorsal digital nerves with or without dorsal branches of the proper digital nerves, can be used to reconstruct thumb...
BACKGROUND
The first dorsal metacarpal artery flap, including dorsal digital nerves with or without dorsal branches of the proper digital nerves, can be used to reconstruct thumb pulp defects with good results. However, it is still unclear whether there are differences in the sensory outcomes between preserving or not preserving the dorsal branches of the proper digital nerves.
METHODS
This retrospective cohort study included 137 thumb pulp defect patients who underwent first dorsal metacarpal artery flap reconstruction procedure from October 2015 to June 2019. Patients were divided into two groups according to whether the dorsal branches of the proper digital nerves were preserved. In the non-preservation group (n = 80), the dorsal digital nerves were included in the flap for sensory reconstruction. In the preservation group (n = 57), the dorsal digital nerves and the dorsal branches of the proper digital nerves of the index finger were included in the flap. The stump of the proper digital nerves in the defect was coaptated to the donor nerves of the flap using the end-to-end fashion. At the last follow-up, static two-point discrimination, Semmes-Weinstein monofilament scores, pain, cold intolerance of the reconstructed finger, and patient satisfaction in both groups were compared.
RESULTS
All patients were followed up for at least 17 months. No significant differences were found regarding pain of thumb pulp, static two-point discrimination, Semmes-Weinstein monofilament score, cold intolerance in the injured finger, and patient satisfaction. The non-preservation group presented slightly shorter operative times (p < 0.05).
CONCLUSION
There are no differences at 2 years in postoperative clinical outcomes when dorsal digital nerves are used to reconstruct flap sensation regardless of preservation of the dorsal branches of the proper digital nerves in the first dorsal metacarpal artery flap.
LEVEL OF EVIDENCE
Level III, retrospective comparative study.
Topics: Adult; Female; Finger Injuries; Humans; Male; Middle Aged; Plastic Surgery Procedures; Retrospective Studies; Soft Tissue Injuries; Surgical Flaps; Thumb; Treatment Outcome; Young Adult
PubMed: 34794478
DOI: 10.1186/s13018-021-02838-z -
Cortex; a Journal Devoted To the Study... Jun 2023Successful action comprehension requires the integration of motor information and semantic cues about objects in context. Previous evidence suggests that while motor...
Successful action comprehension requires the integration of motor information and semantic cues about objects in context. Previous evidence suggests that while motor features are dorsally encoded in the fronto-parietal action observation network (AON); semantic features are ventrally processed in temporal structures. Importantly, these dorsal and ventral routes seem to be preferentially tuned to low (LSF) and high (HSF) spatial frequencies, respectively. Recently, we proposed a model of action comprehension where we hypothesized an additional route to action understanding whereby coarse LSF information about objects in context is projected to the dorsal AON via the prefrontal cortex (PFC), providing a prediction signal of the most likely intention afforded by them. Yet, this model awaits for experimental testing. To this end, we used a perturb-and-measure continuous theta burst stimulation (cTBS) approach, selectively disrupting neural activity in the left and right PFC and then evaluating the participant's ability to recognize filtered action stimuli containing only HSF or LSF. We find that stimulation over PFC triggered different spatial-frequency modulations depending on lateralization: left-cTBS and right-cTBS led to poorer performance on HSF and LSF action stimuli, respectively. Our findings suggest that left and right PFC exploit distinct spatial frequencies to support action comprehension, providing evidence for multiple routes to social perception in humans.
Topics: Humans; Comprehension; Prefrontal Cortex; Cues; Transcranial Magnetic Stimulation
PubMed: 37030047
DOI: 10.1016/j.cortex.2023.01.015 -
Cureus Jul 2023Background The purpose of the study was to provide a practical landmark for localizing the dorsal branch of the ulnar artery and nerve, to approach for microsurgical...
Background The purpose of the study was to provide a practical landmark for localizing the dorsal branch of the ulnar artery and nerve, to approach for microsurgical flaps, for harvesting nerve grafts and also to avoid these nerves during insertion of wrist arthroscopy portals. Material and methods Forty adult cadaveric upper limbs (20 right and 20 left) were dissected for localizing the dorsal branches of the ulnar artery and nerve. The ramification patterns of the nerve were mapped. The wrist arthroscopy portals are located radial and ulnar to the tendon of extensor carpi ulnaris at the level of the wrist joint, and their designated names are '6R & 6U', respectively. The distance of branches of the nerve from the 6U and 6R portals for wrist arthroscopy was recorded. Results The present study has delineated a subcutaneous dorsomedial triangular area in the distal forearm. The construction of this triangle uses palpable landmarks, i.e. pisiform bone, styloid process and subcutaneous border of the ulna. The measure of the sides of the triangle uses proportion rather than absolute measurements and hence is person specific. The dorsal branches of the ulnar nerve and artery are consistently given off in the triangle's upper third and middle third, respectively. Four branching patterns have been mapped, with one dominant pattern in 67.5% of limbs. In three-fourths of cases, one branch of the dorsal branch of the ulnar nerve consistently overlies the 6U portal and hence runs a higher risk of injury. Conclusion The study suggests more practical, accurate, reliable and consistent surface landmarks for the localization of the dorsal branch of the ulnar artery and nerve for reconstructive microsurgery for distal hand defects.
PubMed: 37593310
DOI: 10.7759/cureus.41981 -
Cells Jan 2022The ventricular-subventricular zone (V-SVZ) is a postnatal germinal niche. It holds a large population of neural stem cells (NSCs) that generate neurons and...
The ventricular-subventricular zone (V-SVZ) is a postnatal germinal niche. It holds a large population of neural stem cells (NSCs) that generate neurons and oligodendrocytes for the olfactory bulb and (primarily) the corpus callosum, respectively. These NSCs are heterogeneous and generate different types of neurons depending on their location. Positional identity among NSCs is thought to be controlled in part by intrinsic pathways. However, extrinsic cell signaling through the secreted ligand Sonic hedgehog (Shh) is essential for neurogenesis in both the dorsal and ventral V-SVZ. Here we used a genetic approach to investigate the role of the transcription factors GLI2 and GLI3 in the proliferation and cell fate of dorsal and ventral V-SVZ NSCs. We find that while GLI3 is expressed in stem cell cultures from both dorsal and ventral V-SVZ, the repressor form of GLI3 is more abundant in dorsal V-SVZ. Despite this high dorsal expression and the requirement for other Shh pathway members, GLI3 loss affects the generation of ventrally-, but not dorsally-derived olfactory interneurons in vivo and does not affect trilineage differentiation in vitro. However, loss of GLI3 in the adult dorsal V-SVZ in vivo results in decreased numbers of OLIG2-expressing progeny, indicating a role in gliogenesis.
Topics: Adult Stem Cells; Animals; Cell Differentiation; Cells, Cultured; Interneurons; Lateral Ventricles; Mice; Nerve Tissue Proteins; Neural Stem Cells; Oligodendrocyte Transcription Factor 2; Smoothened Receptor; Zinc Finger Protein Gli3
PubMed: 35053334
DOI: 10.3390/cells11020218 -
Frontiers in Cell and Developmental... 2022Dorsal closure is a prominent morphogenetic process during embryogenesis, which involves two epithelial tissues, that is, the squamous amnioserosa and the columnar...
Dorsal closure is a prominent morphogenetic process during embryogenesis, which involves two epithelial tissues, that is, the squamous amnioserosa and the columnar lateral epidermis. Non-muscle myosin II-driven constriction in the amnioserosa leads to a decrease in the apical surface area and pulls on the adjacent lateral epidermis, which subsequently moves dorsally. The pull by the amnioserosa becomes obvious in an elongation of the epidermal cells, especially of those in the first row. The contribution of the epidermal cell elongation has remained unclear to dorsal closure. Cell elongation may be a mere passive consequence or an active response to the pulling by the amnioserosa. Here, we found that the lateral epidermis actively responds. We analyzed tensions within tissues and cell junctions by laser ablation before and during dorsal closure, the elliptical and dorsal closure stages, respectively. Furthermore, we genetically and optochemically induced chronic and acute cell contraction, respectively. In this way, we found that tension in the epidermis increased during dorsal closure. A correspondingly increased tension was not observed at individual junctions, however. Junctional tension even decreased during dorsal closure in the epidermis. We strikingly observed a strong increase of the microtubule amount in the epidermis, while non-muscle myosin II increased in both tissues. Our data suggest that the epidermis actively antagonizes the pull from the amnioserosa during dorsal closure and the increased microtubules might help the epidermis bear part of the mechanical force.
PubMed: 35652100
DOI: 10.3389/fcell.2022.865397 -
Journal of Neurosurgery. Case Lessons Jan 2023Ganglioneuroma is a benign and well-differentiated tumor derived from neural crest cells, which occurs infrequently, with most patients being female and adolescents....
BACKGROUND
Ganglioneuroma is a benign and well-differentiated tumor derived from neural crest cells, which occurs infrequently, with most patients being female and adolescents. While predilection sites are the posterior mediastinum and retroperitoneal cavity, ganglioneuroma originating from the dorsal root ganglion is very rare. Here the authors report a case with C2 dorsal root ganglion-derived ganglioneuroma with some literature review.
OBSERVATIONS
A 45-year-old male patient complained of persistent right-side throbbing occipital headache for more than a year. Magnetic resonance imaging (MRI) of the cervical spine revealed a dumbbell-shaped intradural extramedullary tumor from the C2 posterior surface of the odontoid to right C1-2 intervertebral foramen with high T2- and low T1-weighted signal intensities. The tumor displayed homogeneous contrast enhancement by MRI. The authors suspected schwannoma and performed a tumorectomy for both diagnosis and treatment purposes. Intraoperative findings showed that the tumor originated from the dorsal root ganglion, and pathological examination revealed ganglioneuroma. Immediately after the tumorectomy, the throbbing occipital headache disappeared and the patient was discharged from the hospital without major complications.
LESSONS
Although ganglioneuroma derived from the dorsal root ganglion is very rare, a differential diagnosis of the ganglioneuroma should be made, when schwannoma is suspected.
PubMed: 36647254
DOI: 10.3171/CASE22456 -
Frontiers in Cellular Neuroscience 2021Dorsal and median raphe nuclei (DR and MR, respectively) are members of the reticular activating system and play important role in the regulation of the...
Dorsal and median raphe nuclei (DR and MR, respectively) are members of the reticular activating system and play important role in the regulation of the sleep-wakefulness cycle, movement, and affective states. M-current is a voltage-gated potassium current under the control of neuromodulatory mechanisms setting neuronal excitability. Our goal was to determine the proportion of DR and MR serotonergic neurons possessing M-current and whether they are organized topographically. Electrophysiological parameters of raphe serotonergic neurons influenced by this current were also investigated. We performed slice electrophysiology on genetically identified serotonergic neurons. Neurons with M-current are located rostrally in the DR and dorsally in the MR. M-current determines firing rate, afterhyperpolarization amplitude, and adaptation index (AI) of these neurons, but does not affect input resistance, action potential width, and high threshold oscillations.These findings indicate that M-current has a strong impact on firing properties of certain serotonergic neuronal subpopulations and it might serve as an effective contributor to cholinergic and local serotonergic neuromodulatory actions.
PubMed: 33716672
DOI: 10.3389/fncel.2021.614947 -
Trauma Case Reports Apr 2023Bennet's fracture represents one of the most common injuries of the hand district, involving the base of the thumb, and it is affects children and elderly patients the...
Bennet's fracture represents one of the most common injuries of the hand district, involving the base of the thumb, and it is affects children and elderly patients the most. The fracture is caused by direct axial trauma to a partially flexed first metacarpal and it is always intra-articular: the fracture line separates the palmar ulnar aspect of the first metacarpal base from the remaining first metacarpal. The fracture pattern is such that the first metacarpal shaft moves dorsally, proximally, and radially due to the pull of the abductor pollicis longus, extensor pollicis longus, extensor pollicis brevis, and the adductor pollicis brevis, which remain attached to the fracture fragment. The surgical treatment consists of closed reduction with percutaneous pinning or open reduction with either pins or interfragmentary screws. The decision to treat these fractures with either open reduction or closed reduction is still a matter of debate. To the best of our knowledge, there are no cases of bilateral Bennett's fracture reported in literature. The aim of this paper is to present a rare case of bilateral Bennet's fracture, the decision of two different treatments, and the good clinical outcomes.
PubMed: 36851906
DOI: 10.1016/j.tcr.2023.100786