Many organisms capture or sense sunlight using rhodopsin pigments, which are integral membrane proteins that bind retinal chromophores. Rhodopsins comprise two distinct protein families , type-1 (microbial rhodopsins) and type-2 (animal rhodopsins). The two families share similar topologies and contain seven transmembrane helices that form a pocket in which retinal is linked covalently as a protonated Schiff base to a lysine at the seventh transmembrane helix. Type-1 and type-2 rhodopsins show little or no sequence similarity to each other, as a consequence of extensive divergence from a common ancestor or convergent evolution of similar structures . Here we report a previously unknown and diverse family of rhodopsins-which we term the heliorhodopsins-that we identified using functional metagenomics and that are distantly related to type-1 rhodopsins. Heliorhodopsins are embedded in the membrane with their N termini facing the cell cytoplasm, an orientation that is opposite to that of type-1 or type-2 rhodopsins. Heliorhodopsins show photocycles that are longer than one second, which is suggestive of light-sensory activity. Heliorhodopsin photocycles accompany retinal isomerization and proton transfer, as in type-1 and type-2 rhodopsins, but protons are never released from the protein, even transiently. Heliorhodopsins are abundant and distributed globally; we detected them in Archaea, Bacteria, Eukarya and their viruses. Our findings reveal a previously unknown family of light-sensing rhodopsins that are widespread in the microbial world.

Schizorhodopsins (SzRs), a rhodopsin family first identified in Asgard archaea, the archaeal group closest to eukaryotes, are present at a phylogenetically intermediate position between typical microbial rhodopsins and heliorhodopsins. However, the biological function and molecular properties of SzRs have not been reported. Here, SzRs from Asgardarchaeota and from a yet unknown microorganism are expressed in Escherichia coli and mammalian cells, and ion transport assays and patch clamp analyses are used to demonstrate SzR as a novel type of light-driven inward H+ pump. The mutation of a cytoplasmic glutamate inhibited inward H+ transport, suggesting that it functions as a cytoplasmic H+ acceptor. The function, trimeric structure, and H+ transport mechanism of SzR are similar to that of xenorhodopsin (XeR), a light-driven inward H+ pumping microbial rhodopsins, implying that they evolved convergently. The inward H+ pump function of SzR provides new insight into the photobiological life cycle of the Asgardarchaeota.

The light-dependent ion-transport function of microbial rhodopsin has been widely used in optogenetics for optical control of neural activity. In order to increase the variety of rhodopsin proteins having a wide range of absorption wavelengths, the light absorption properties of various wild-type rhodopsins and their artificially mutated variants were investigated in the literature. Here, we demonstrate that a machine-learning-based (ML-based) data-driven approach is useful for understanding and predicting the light-absorption properties of microbial rhodopsin proteins. We constructed a database of 796 proteins consisting of microbial rhodopsin wildtypes and their variants. We then proposed an ML method that produces a statistical model describing the relationship between amino-acid sequences and absorption wavelengths and demonstrated that the fitted statistical model is useful for understanding colour tuning rules and predicting absorption wavelengths. By applying the ML method to the database, two residues that were not considered in previous studies are newly identified to be important to colour shift.

Bearden et al 1 reported an impressive antiepileptic effect of quinidine on 1 patient initiated at 25 months with KCNT1 (c.1283G>A; p.Arg428Gly, R428Q) mutation diagnosed with epilepsy of infancy with migrating focal seizures (EIMFS). R428Q was proven to be a gain-of-function pathogenic KCNT1 mutation, with an increase of current observed in electrophysiological study. 2 The reported patient was completely seizure free and showed improved psychomotor development. Due to the promising effect, we started the therapy on an unclassified early onset epileptic encephalopathy patient who had the same R428Q mutation.The patient is currently a 6-year-old male who was born at term with no family history of neurologic disorders. He was brought to us at 6 weeks of life with seizures characterized by a brief episode of staring and right hemiclonic seizures. Interictal electroencephalogram (EEG) showed multifocal sharp waves, and ictal EEG at 3 months displayed rhythmic delta-wave activity in bilateral occipital areas. Intracranial magnetic resonance imaging was normal at 1 month. At 4 years, whole exome sequencing revealed a heterozygous de novo KCNT1 R428Q mutation by a previously published method (Patient 11). 3Seizure control was refractory to multiple antiepileptic drugs, with seizure frequency peaking at 200 times/day. Ketogenic diet and vagal nerve stimulation reduced the seizure frequency to half. He was bedridden with poor neurodevelopment. Quinidine therapy was started at 5 years. The dose was titrated slowly, adjusted by monitoring the trough serum levels of quinidine at the range of 1.5 to 3.0 lg/ml. The patient was monitored for side effects, and no major adverse event was noted. Frequency of daily seizures was recorded, with monthly seizure frequency before and after quinidine therapy presented in the Figure. Contrary to expectations, quinidine was ineffective in seizure reduction. Seizure frequency per month after quinidine therapy was 103 6 27.7, compared to 106 6 13.3 for the same period before.In a recent literature concerning KCNT1-positive epilepsies, whereas quinidine showed 80% seizure reduction in one 3-year-old EIMFS patient (K629N), it was ineffective in an 11-year-old patient with unclassified epilepsy (Y796H).4 Therapy initiation at a later age and electroclinical syndrome other than EIFMS are possible reasons for poor response to quinidine in our case. Earlier FIGURE: Seizure frequency per month before and after quinidine therapy for a period of 8 months is presented. Seizure frequency was documented by reviewing the patient's daily seizure calendar, kept reliably by the patient's family. Quinidine therapy was started on X month with slow titration. Quinidine dose used (mg/kg/day) is shown in a line graph; the maximum dosage used was 73mg/kg/day. Therapeutic drug monitoring of quinidine was performed, and the trough serum levels were adjusted between 1.5 and 3.0 lg/ml (not shown). Effective seizure reduction compared to the same period before therapy was not observed.502 V C 2016 American Neurologic...

Microbial rhodopsins are photoreceptive membrane proteins that transport various ions using light energy. While they are widely used in optogenetics to optically control neuronal activity, rhodopsins that function with longer-wavelength light are highly demanded because of their low phototoxicity and high tissue penetration. Here, we achieve a 40-nm red-shift in the absorption wavelength of a sodium-pump rhodopsin (KR2) by altering dipole moment of residues around the retinal chromophore (KR2 P219T/S254A) without impairing its ion-transport activity. Structural differences in the chromophore of the red-shifted protein from that of the wildtype are observed by Fourier transform infrared spectroscopy. QM/MM models generated with an automated protocol show that the changes in the electrostatic interaction between protein and chromophore induced by the amino-acid replacements, lowered the energy gap between the ground and the first electronically excited state. Based on these insights, a natural sodium pump with red-shifted absorption is identified from Jannaschia seosinensis .

Background We investigated the feasibility and safety of a video-based telemedicine system, delivered via a tablet, in Parkinson's disease (PD). Methods In a randomized, crossover, open-label pilot trial, we compared a telemedicine period (regular visits every two months with intermediate video calls via an iPad mini) with a control period (regular visits every two months), both lasting 6 months. We included 10 patients diagnosed with PD according to the British Brain Bank criteria, aged 20–75 years. The primary outcome was the PD questionnaire summary index (PDQ-39 SI). Secondary outcomes included the Hoehn and Yahr Stage and scores on the Unified PD Rating Scale (UPDRS) part I–IV, Beck Depression Inventory (BDI), and visual analog scale for satisfaction. Results Both study periods were completed by 10 patients with PD. Friedman's test revealed that there were no significant differences between the two periods in primary and secondary outcomes (p > 0.05). With respect to visual analog scale scores for satisfaction, participants indicated high satisfaction with the telemedicine system. The number of extra hospital visits and phone calls did not differ between the periods. There were no adverse events or side effects. Conclusions We observed that a telemedicine system delivered via a tablet could successfully be used by patients as a part of their care. Further studies investigating the use of telemedicine to replace in-person visits are warranted. This trial is registered with UMIN000015536.

BackgroundMyelin-oligodendrocyte glycoprotein antibody (MOG antibodies) was found in various demyelinated diseases. This is the first report of a patient with longitudinally extensive transverse myelitis with an extremely high titer of MOG antibodies after an influenza infection. This case supports the view that MOG antibodies are linked to longitudinally extensive transverse myelitis and that influenza infection might trigger the MOG antibodies.Case presentationA 32-year-old healthy male developed high fever, dysesthesia and paraesthesia below the C2 area, muscle weakness of the bilateral lower extremities, and urinary retention ten days after an influenza type A infection. Magnetic resonance imaging revealed a longitudinal lesion in the spinal cord extending from C2 to the spinal conus. There were no lesions in the brain or optic nerves. Established cell-based immunoassays revealed that he was positive for MOG antibodies (titer = 65,536) and negative for anti-aquaporin 4 antibodies (AQP4 antibodies). He fully recovered after steroid pulse therapy followed by 60 mg prednisolone.ConclusionThis is the first report of influenza A-associated longitudinally extensive transverse myelitis with a high titer anti-MOG antibodies. Our case report supports a relationship between anti-MOG antibodies and longitudinally extensive transverse myelitis, which was triggered by influenza infection. Further studies are needed to establish the clinical significance of anti-MOG antibodies for diagnosis, treatment, and prognosis.

ABSTRACT. Preweaning mortality risks, recorded death reasons and related factors for preweaning mortality were studied in 105 breeding herds. Preweaning mortality risk at the herd level was calculated as the difference between the number of pigs born alive in farrowed litters and the number of weaned pigs divided by the number of pigs born alive in litters that farrowed and weaned. The mean of annual preweaning mortality risk was 10.7%. In regression analysis, higher mortality risks were associated with higher parity at farrowing, greater numbers of pigs born alive, and longer lactation length. The period from July to September had a higher mortality risk than that from April to June. The means of cause-specific proportional mortality ratios (PMR) in trauma with low viability and scours were 80.4 and 6.2%, respectively. Sows with pig age 0-1 day during lactation had the highest daily PMR. Sows with pig age 0 to 7 days had higher PMR due to trauma and low variability than those with pig age 8 days older. Sows with pig age over 7 days had higher PMR due to scours than those with pig age 0-7 days. Careful management at farrowing and in early lactation on high parity sows with large litters should be considered to prevent piglets from death due to trauma and low viability, and appropriate herd health programs should be implemented for reducing preweaning mortality due to scours during late lactation.