Subtle changes in the membrane potential of pulmonary arterial smooth muscle cells (PASMCs) are pivotal for controlling pulmonary vascular tone, e.g., for initiating Hypoxic Pulmonary Vasoconstriction, a vital mechanism of the pulmonary circulation. In our study, we evaluated the ability of the fluorescence resonance energy transfer (FRET)-based voltage-sensor Mermaid to detect such subtle changes in membrane potential. Mouse PASMCs were isolated and transduced with Mermaid-encoding lentiviral vectors before the acceptor/donor emission ratio was assessed via live cell FRET-imaging. Mermaid\'s sensitivity was tested by applying specific potassium chloride (KCl) concentrations. These KCl concentrations were previously validated by patch clamp recordings to induce depolarization with predefined amplitudes that physiologically occur in PASMCs. Mermaid\'s emission ratio dose-dependently increased upon depolarization with KCl. However, Mermaid formed unspecific intracellular aggregates, which limited the usefulness of this voltage sensor. When analyzing the membrane rim only to circumvent these unspecific signals, Mermaid was not suitable to resolve subtle changes in the membrane potential of ≤10 mV. In summary, we found Mermaid to be a suitable alternative for reliably detecting qualitative membrane voltage changes of more than 10 mV in primary mouse PASMCs. However, one should be aware of the limitations associated with this voltage sensor.

Sirenomelia, also known as \"mermaid syndrome\" or \"mermaid baby syndrome,\" is a very rare congenital disorder. The major anomaly in this syndrome is the fusion of the lower legs, giving it a mermaid-like appearance. This syndrome consists of a range of abnormalities affecting various systems, such as the digestive, genitourinary, and musculoskeletal systems. On the basis of the severity of the syndrome, the fetus may have a single fused bone or entirely absent bones in place of a normal pair of distinct bones. In major cases, mermaid syndrome leads to stillbirths. Its occurrence in monozygotic twins is much greater than in dizygotic twins or in a single fetus. The syndrome is believed to mainly occur in cases of maternal age less than 20 years or more than 40 years, women suffering from maternal diabetes, and prenatal exposure to retinoic acid, cocaine, and water contaminated by landfills. A 22-year-old pregnant female was admitted with a history of amenorrhea for nine months (full-term twin pregnancy) and oligohydramnios for a caesarian section. This was the patient\'s second pregnancy. A cesarean section was done as instructed by the gynecologist. The patient delivered twin babies. In this twin pregnancy, the first baby was normal and healthy, while the second baby was stillborn and suffered from mermaid syndrome.

Optogenetics has a lot of potential to become an effective neuromodulative therapy for clinical applications. Selecting the correct opsin is crucial to have an optimal optogenetic tool. With computational modeling, the neuronal response to the current dynamics of an opsin can be extensively and systematically tested. Unlike electrical stimulation where the effect is directly defined by the applied field, the stimulation in optogenetics is indirect, depending on the selected opsin\'s non-linear kinetics. With the continuous expansion of opsin possibilities, computational studies are difficult due to the need for an accurate model of the selected opsin first. To this end, we propose a double two-state opsin model as alternative to the conventional three and four state Markov models used for opsin modeling. Furthermore, we provide a fitting procedure, which allows for autonomous model fitting starting from a vast parameter space. With this procedure, we successfully fitted two distinctive opsins (ChR2(H134R) and MerMAID). Both models are able to represent the experimental data with great accuracy and were obtained within an acceptable time frame. This is due to the absence of differential equations in the fitting procedure, with an enormous reduction in computational cost as result. The performance of the proposed model with a fit to ChR2(H134R) was tested, by comparing the neural response in a regular spiking neuron to the response obtained with the non-instantaneous, four state Markov model (4SB), derived by Williams et al. (2013). Finally, a computational speed gain was observed with the proposed model in a regular spiking and sparse Pyramidal-Interneuron-Network-Gamma (sPING) network simulation with respect to the 4SB-model, due to the former having two differential equations less. Consequently, the proposed model allows for computationally efficient optogenetic neurostimulation and with the proposed fitting procedure will be valuable for further research in the field of optogenetics.

Sirenomelia is a rare congenital anomaly characterized by the presence of a median single lower appendage. The affected fetus is popularly referred to as a \"Mermaid baby,\" due to the uncanny resemblance to the fictious fable character. The manifestation is a result of the merger of the lower limbs with variable fusion or complete absence of bones. Sirenomelia is universally fatal due to the associated lethal anomalies involving the internal organs, which are usually part of the VACTER or VACTERL complex. However, this sirenomelia-afflicted fetus is unique in being associated with VACTERL as well as congenital hydrocephalus.

We are reporting a rare case of sirenomelia with oesophageal atresia. Sirenomelia is a lethal sporadic defect of which lower gastrointestinal tract anomalies are characteristic findings. Respiratory and upper gastrointestinal tract malformations like oesophageal atresia occur in about 20-35% of cases. Though its occurrence has been described, it has been reported only rarely. This report aims at describing this uncommon association along with its histological features.