µ1‐Opioid receptors in the dorsomedial and ventrolateral columns of the periaqueductal grey matter are critical for the enhancement of post‐ictal antinociception

Generalised tonic and tonic–clonic seizures are followed by significant increase in nociceptive thresholds in both laboratory animals and humans. The endogenous opioid peptides play a role in antinociceptive signalling, and the periaqueductal grey matter (PAG) is recruited to induce analgesia. Thus, the aim of this investigation was to evaluate the role of µ₁‐opioid receptors in the dorsomedial (dm) and ventrolateral (vl) columns of PAG in post‐ictal antinociception. Pentylenetetrazole (PTZ; 64 mg/kg), which is an ionotropic GABA‐mediated Cl^? influx antagonist, was intraperitoneally (IP) administered to induce tonic–clonic seizures in Wistar rats. The tail‐flick test was used to measure the nociceptive threshold. Microinjections of naltrexone (5.0 µg/0.2 µL), which is a non‐selective opioid receptor antagonist, in both dmPAG and vlPAG decreased the tonic–clonic seizure‐induced antinociception in seizing animals from 10 to 120 min after seizures. Furthermore, microinjections of the µ₁‐opioid receptor‐selective antagonist naloxonazine (5.0 µg/0.2 µL) into the dmPAG decreased post‐ictal antinociception immediately after convulsive reactions and from 10 to 90 min after seizures. However, vlPAG‐pretreatment with naloxonazine at the same concentration decreased the post‐ictal antinociception 30 min after the onset of tonic–clonic seizures and the nociceptive threshold returned to basal values 120 min after seizures. These findings indicate that µ₁‐opioid receptor‐signalling mechanisms in both dmPAG and vlPAG play a relevant role in the organisation of post‐ictal antinociception. In addition, µ₁‐opioid receptors in the dmPAG rather than in vlPAG seem to be more critically recruited during the antinociception induced by generalised tonic–clonic seizures.     

DFT study of superhalogen and superalkali doped graphitic carbon nitride and its non-linear optical properties

DFT calculations are carried out to investigate nonlinear optical (NLO) properties of superhalogen (BCl₄) and superalkali (NLi₄) doped graphitic carbon nitride (GCN). It is noted that the geometries of doped GCN are sufficiently stable. The energy gap for GCN is 3.89 and it reduces to 0.53 eV in our designed molecule G4. Change in the dipole and transition dipole moment is observed along with small transition energies which are responsible for higher hyperpolarizabilities. Doped GCN has larger first and second hyperpolarizabilities which are basic requirements for NLO response. The second hyperpolarizability of GCN enhances from 1.59 × 10⁴ to 2.53 × 10⁸ au when doping with BCl₄ and NLi₄. TD-DFT calculations show the absorption maxima of doped GCN range from 700 nm to 1350 nm. EDDM analysis provides information on electronic distribution from excited to ground state. All these consequences show doped GCN can be a promising NLO material.

DFT calculations are carried out to investigate nonlinear optical (NLO) properties of superhalogen (BCl₄) and superalkali (NLi₄) doped graphitic carbon nitride (GCN).     

CD166pos Subpopulation From Differentiated Human ES and iPS Cells Support Repair of Acute Lung Injury

Previous efforts to derive lung progenitor cells from human embryonic stem (hES) cells using embryoid body formation or stromal feeder cocultures had been limited by low efficiencies. Here, we report a step-wise differentiation method to drive both hES and induced pluripotent stem (iPS) cells toward the lung lineage. Our data demonstrated a 30% efficiency in generating lung epithelial cells (LECs) that expresses various distal lung markers. Further enrichment of lung progenitor cells using a stem cell marker, CD166 before transplantation into bleomycin-injured NOD/SCID mice resulted in enhanced survivability of mice and improved lung pulmonary functions. Immunohistochemistry of lung sections from surviving mice further confirmed the specific engraftment of transplanted cells in the damaged lung. These cells were shown to express surfactant protein C, a specific marker for distal lung progenitor in the alveoli. Our study has therefore demonstrated the proof-of-concept of using iPS cells for the repair of acute lung injury, demonstrating the potential usefulness of using patient''s own iPS cells to prevent immune rejection which arise from allogenic transplantation.     

Novel homozygous sequence variants in the GDF5 gene underlie acromesomelic dysplasia type‐grebe in consanguineous families

Acromesomelic dysplasia Grebe type (AMDG) is characterized by severe knob like non‐functional fingers and short acromesomelic limbs, and is inherited in an autosomal recessive manner. Disease causing sequence variants in the GDF5 (Growth Differentiation Factor 5) gene located on chromosome 20q11.22 are responsible for causing AMDG. In the study, presented here, two consanguineous families with AMDG were clinically and genetically characterized. After establishing linkage in the two families (A and B) to GDF5 gene on chromosome 20q11.22, Sanger DNA sequencing was performed in all available affected and unaffected members. Sequence analysis of the GDF5 gene revealed two novel variants including a duplication (c.157_158dupC, p.Leu53Profs*41) in family A, and a nonsense (p.Trp291*) in family B. Our findings extend the body of evidence that supports the importance of GDF5 in the development of limbs.     

Mediastinal impalement with a fibreglass sheet

Mediastinal impalement injuries are uncommon and often fatal. There have been very few reported cases of survival following mediastinal impalement. Patients who present with these injuries always undergo operative intervention regardless of their underlying haemodynamic status or associated injuries. We herein present a case of mediastinal impalement injury, where a sheet of fibreglass had fractured the manubrium and entered thffige anterior mediastinum with no associated great vessel injury. The fibreglass sheet was removed via a partial sternotomy and the patient made an uneventful postoperative recovery.     

A novel nonsense variant in EXOC8 underlies a neurodevelopmental disorder

neurogenetics - Human exocyst complex is an evolutionary conserved multimeric complex composed of proteins encoded by eight genes EXOC1-EXOC8. It is known that the exocyst complex plays a role in...