Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 60
Filter
1.
Proc Natl Acad Sci U S A ; 121(21): e2406565121, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38753507

ABSTRACT

While depolarization of the neuronal membrane is known to evoke the neurotransmitter release from synaptic vesicles, hyperpolarization is regarded as a resting state of chemical neurotransmission. Here, we report that hyperpolarizing neurons can actively signal neural information by employing undocked hemichannels. We show that UNC-7, a member of the innexin family in Caenorhabditis elegans, functions as a hemichannel in thermosensory neurons and transmits temperature information from the thermosensory neurons to their postsynaptic interneurons. By monitoring neural activities in freely behaving animals, we find that hyperpolarizing thermosensory neurons inhibit the activity of the interneurons and that UNC-7 hemichannels regulate this process. UNC-7 is required to control thermotaxis behavior and functions independently of synaptic vesicle exocytosis. Our findings suggest that innexin hemichannels mediate neurotransmission from hyperpolarizing neurons in a manner that is distinct from the synaptic transmission, expanding the way of neural circuitry operations.


Subject(s)
Caenorhabditis elegans Proteins , Caenorhabditis elegans , Interneurons , Neurons , Synaptic Transmission , Animals , Caenorhabditis elegans/physiology , Caenorhabditis elegans/metabolism , Caenorhabditis elegans Proteins/metabolism , Caenorhabditis elegans Proteins/genetics , Synaptic Transmission/physiology , Interneurons/metabolism , Interneurons/physiology , Neurons/physiology , Neurons/metabolism , Synaptic Vesicles/metabolism , Synaptic Vesicles/physiology , Taxis Response/physiology , Connexins/metabolism , Connexins/genetics , Membrane Proteins
2.
J Med Invest ; 70(3.4): 471-475, 2023.
Article in English | MEDLINE | ID: mdl-37940534

ABSTRACT

The purpose of this study is to evaluate the results and intraoperative or postoperative complications of primary total hip arthroplasty (THA) using a contemporary tapered wedge titanium femoral component. A total of 213 THAs in 187 patients were followed up more than 5 years (mean, 102 months ; range, 60-150). The mean age at surgery was 64.2 years (range, 20?89 years). These patients were clinically evaluated using the JOA scoring system and radiographically host bone reactions around the implants, as well as femoral loosening. The mean JOA score improved from 49 (range, 21?75) to 92 (range, 59?100). All 12 patients with poor results (JOA < 75) coexisted with cerebral, spinal, joint, and musculoskeletal disorders. At the final follow-up, implant survival was 100%. Complications occurred in 23 hips. They consisted of 12 hips with intra-operative fractures, 2 hips with sciatic nerve palsy, one hip with infections, 3 hips with recurrent dislocations, and 8 hips with aseptic cup loosening. In conclusion, we have shown excellent survival rate of the contemporary tapered wedge stem in primary THA ; however, patients with coexisting diseases could not acquire sufficient improvement in hip function and ambulatory ability. J. Med. Invest. 70 : 471-475, August, 2023.


Subject(s)
Arthroplasty, Replacement, Hip , Hip Prosthesis , Humans , Young Adult , Adult , Arthroplasty, Replacement, Hip/adverse effects , Arthroplasty, Replacement, Hip/methods , Titanium , Follow-Up Studies , Prosthesis Design , Reoperation , Treatment Outcome , Retrospective Studies
3.
Elife ; 122023 05 30.
Article in English | MEDLINE | ID: mdl-37252859

ABSTRACT

The causality and mechanism of dietary effects on brain aging are still unclear due to the long time scales of aging. The nematode Caenorhabditis elegans has contributed to aging research because of its short lifespan and easy genetic manipulation. When fed the standard laboratory diet, Escherichia coli, C. elegans experiences an age-dependent decline in temperature-food associative learning, called thermotaxis. To address if diet affects this decline, we screened 35 lactic acid bacteria as alternative diet and found that animals maintained high thermotaxis ability when fed a clade of Lactobacilli enriched with heterofermentative bacteria. Among them, Lactobacillus reuteri maintained the thermotaxis of aged animals without affecting their lifespan and motility. The effect of Lb. reuteri depends on the DAF-16 transcription factor functioning in neurons. Furthermore, RNA sequencing analysis revealed that differentially expressed genes between aged animals fed different bacteria were enriched with DAF-16 targets. Our results demonstrate that diet can impact brain aging in a daf-16-dependent manner without changing the lifespan.


Subject(s)
Caenorhabditis elegans Proteins , Caenorhabditis elegans , Animals , Caenorhabditis elegans/physiology , Caenorhabditis elegans Proteins/genetics , Aging/physiology , Longevity/physiology , Diet , Escherichia coli/physiology , Forkhead Transcription Factors/genetics
4.
Neurosci Res ; 188: 10-27, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36336147

ABSTRACT

Elucidating how individual neurons encode and integrate sensory information to generate a behavior is crucial for understanding neural logic underlying sensory-dependent behavior. In the nematode Caenorhabditis elegans, information flow from sensory input to behavioral output is traceable at single-cell level due to its entirely solved neural connectivity. C. elegans processes the temperature information for regulating behavior consisting of undulatory posture dynamics in a circuit including two thermosensory neurons AFD and AWC, and their postsynaptic interneuron AIY. However, how the information processing in AFD-AWC-AIY circuit generates the posture dynamics remains elusive. To quantitatively evaluate the posture dynamics, we introduce locomotion entropy, which measures bandwidth of the frequency spectrum of the undulatory posture dynamics, and assess how the motor pattern fluctuates. We here found that AWC disorders the information processing in AFD-AWC-AIY circuit for regulating temperature-evoked posture dynamics. Under slow temperature ramp-up, AWC adjusts AFD response, whereby broadening the temperature range in which animals exhibit fluctuating posture undulation. Under rapid temperature ramp-up, AWC increases inter-individual variability in AIY activity and the fluctuating posture undulation. We propose that a compact nervous system recruits a sensory neuron as a fluctuation inducer for regulating sensory-dependent behavior.


Subject(s)
Caenorhabditis elegans Proteins , Caenorhabditis elegans , Animals , Caenorhabditis elegans/physiology , Temperature , Sensory Receptor Cells , Posture
5.
PLoS One ; 17(12): e0278343, 2022.
Article in English | MEDLINE | ID: mdl-36472979

ABSTRACT

Living organisms including bacteria, plants and animals sense ambient temperature so that they can avoid noxious temperature or adapt to new environmental temperature. A nematode C. elegans can sense innocuous temperature, and navigate themselves towards memorize past cultivation temperature (Tc) of their preference. For this thermotaxis, AFD thermosensory neuron is pivotal, which stereotypically responds to warming by increasing intracellular Ca2+ level in a manner dependent on the remembered past Tc. We aimed to reveal how AFD encodes the information of temperature into neural activities. cGMP synthesis in AFD is crucial for thermosensation in AFD and thermotaxis behavior. Here we characterized the dynamic change of cGMP level in AFD by imaging animals expressing a fluorescence resonance energy transfer (FRET)-based cGMP probe specifically in AFD and found that cGMP dynamically responded to both warming and cooling in a manner dependent on past Tc. Moreover, we characterized mutant animals that lack guanylyl cyclases (GCYs) or phosphodiesterases (PDEs), which synthesize and hydrolyze cGMP, respectively, and uncovered how GCYs and PDEs contribute to cGMP and Ca2+ dynamics in AFD and to thermotaxis behavior.


Subject(s)
Caenorhabditis elegans , Neurons , Animals , Caenorhabditis elegans/genetics
6.
G3 (Bethesda) ; 12(11)2022 11 04.
Article in English | MEDLINE | ID: mdl-36102820

ABSTRACT

Animals integrate sensory stimuli presented at the past and present, assess the changes in their surroundings and navigate themselves toward preferred environment. Identifying the neural mechanisms of such sensory integration is pivotal to understand how the nervous system generates perception and behavior. Previous studies on thermotaxis behavior of Caenorhabditis elegans suggested that a single thermosensory neuron AFD plays an important role in integrating the past and present temperature information and is essential for the neural computation that drives the animal toward the preferred temperature region. However, the molecular mechanisms by which AFD executes this neural function remained elusive. Here we report multiple forward genetic screens to identify genes required for thermotaxis. We reveal that kin-4, which encodes the C. elegans homolog of microtubule-associated serine threonine kinase, plays dual roles in thermotaxis and can promote both cryophilic and thermophilic drives. We also uncover that a thermophilic defect of mutants for mec-2, which encodes a C. elegans homolog of stomatin, can be suppressed by a loss-of-function mutation in the gene crh-1, encoding a C. elegans homolog CREB transcription factor. Expression of crh-1 in AFD restored the crh-1-dependent suppression of the mec-2 thermotaxis phenotype, indicating that crh-1 can function in AFD to regulate thermotaxis. Calcium imaging analysis from freely moving animals suggest that mec-2 and crh-1 regulate the neuronal activity of the AIY interneuron, a postsynaptic partner of the AFD neuron. Our results suggest that a stomatin family protein can control the dynamics of neural circuitry through the CREB-dependent transcriptional regulation within a sensory neuron.


Subject(s)
Caenorhabditis elegans Proteins , Taxis Response , Animals , Caenorhabditis elegans/metabolism , Protein Serine-Threonine Kinases/genetics , Caenorhabditis elegans Proteins/genetics , Caenorhabditis elegans Proteins/metabolism , Sensory Receptor Cells/metabolism , Temperature , Microtubules/metabolism , Behavior, Animal/physiology , Transcription Factors/metabolism
7.
Indian J Orthop ; 56(7): 1234-1239, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35813550

ABSTRACT

Introduction: Total hip arthroplasty is a very effective reconstructive surgery but is often associated with massive perioperative bleeding, which leads to anemia. Tranexamic acid (TXA) minimizes bleeding and the need for blood transfusion. However, no universal standard TXA dosing regimen has been established. The objectives of this study were (1) whether there was a difference in the amount of decrease in perioperative mean hemoglobin (Hb) level between a single topical administration of TXA and intravenous and topical combination administration, and we also investigated whether there was a difference in the amount of decrease in the perioperative mean Hb level due to the difference in the local dose of TXA. Methods: We retrospectively reviewed 292 hips between June 2013 and October 2020. The decrease in Hb level (difference between the preoperative value and the 7-day postoperative value) was used to estimate total perioperative blood loss. The mean perioperative reduction in Hb was compared between hips that received intravenous TXA preoperatively and intra-articular TXA at wound closure (combination administration group) and those that received only intra-articular TXA (single dose group). It was also compared by different local doses of tranexamic acid. Results: The mean reduction in Hb was significantly smaller in the combination administration group than in the single dose group. However, no significant difference was observed due to the difference in the local dose of TXA administered at the time of wound closure. Conclusion: Reducing perioperative bleeding decreases the invasiveness of surgery, which is important from the perspective of medical safety.

8.
PLoS Genet ; 18(6): e1010219, 2022 06.
Article in English | MEDLINE | ID: mdl-35675262

ABSTRACT

Animals detect changes in both their environment and their internal state and modify their behavior accordingly. Yet, it remains largely to be clarified how information of environment and internal state is integrated and how such integrated information modifies behavior. Well-fed C. elegans migrates to past cultivation temperature on a thermal gradient, which is disrupted when animals are starved. We recently reported that the neuronal activities synchronize between a thermosensory neuron AFD and an interneuron AIY, which is directly downstream of AFD, in well-fed animals, while this synchrony is disrupted in starved animals. However, it remained to be determined whether the disruption of the synchrony is derived from modulation of the transmitter release from AFD or from the modification of reception or signal transduction in AIY. By performing forward genetics on a transition of thermotaxis behavior along starvation, we revealed that OLA-1, an Obg-like ATPase, functions in AFD to promote disruption of AFD-AIY synchrony and behavioral transition. Our results suggest that the information of hunger is delivered to the AFD thermosensory neuron and gates transmitter release from AFD to disrupt thermotaxis, thereby shedding light onto a mechanism for the integration of environmental and internal state to modulate behavior.


Subject(s)
Caenorhabditis elegans Proteins , Caenorhabditis elegans , Adenosine Triphosphatases/genetics , Animals , Caenorhabditis elegans/genetics , Caenorhabditis elegans Proteins/genetics , Hunger , Sensory Receptor Cells , Temperature
9.
J Orthop Sci ; 27(3): 648-651, 2022 May.
Article in English | MEDLINE | ID: mdl-35370041

ABSTRACT

BACKGROUND: One-stage bilateral total knee arthroplasty (TKA) has the advantages of a single hospital stay, shorter rehabilitation, and reduced financial burden on patients. However, perioperative bleeding is greater with one-stage bilateral TKA than with unilateral TKA and is more likely to require allogeneic blood transfusion. At our hospital, we normally store autologous blood about 1 month before surgery to reduce the need for allogeneic blood transfusion and avoid its adverse reactions as much as possible. The purpose of this study was to determine the efficacy of preoperative autologous blood storage for patients undergoing one-stage bilateral TKA. METHODS: We retrospectively examined the allogeneic blood transfusion avoidance rate and the perioperative decrease in hemoglobin (Hb) level in 166 patients according to whether or not they had preoperative autologous blood stored. The patients for whom blood was stored were then subdivided according to whether the amount of blood stored was 400 mL or 200 mL. RESULTS: Excluding allogeneic transfusion cases, the mean perioperative decrease in Hb was significantly lower in the patients with stored blood than in those without stored blood (3.5 g/dL vs 4.4 g/dL, p < 0.001). The allogeneic blood transfusion avoidance rate was significantly higher in the group with stored blood (98.5% vs 86.7%, p < 0.01). In the group with stored blood, the transfusion avoidance rate was higher, but not significantly, in the subgroup with 400 mL of blood stored than in those with 200 mL of blood stored (100% vs 97.5%) and the mean perioperative decrease in Hb was 3.5 g/dL in both blood storage volume groups. CONCLUSIONS: Preoperative autologous blood storage can help increase the likelihood of avoiding allogeneic blood transfusion in patients undergoing one-stage bilateral TKA.


Subject(s)
Arthroplasty, Replacement, Knee , Hematopoietic Stem Cell Transplantation , Arthroplasty, Replacement, Knee/adverse effects , Blood Loss, Surgical , Blood Preservation , Blood Transfusion , Hemoglobins , Humans , Retrospective Studies
10.
Case Rep Orthop ; 2021: 8849929, 2021.
Article in English | MEDLINE | ID: mdl-34094609

ABSTRACT

Periprosthetic joint infection (PJI) caused by coagulase-negative staphylococci (CNS) can be a mild, persisting infection. Although heterotopic ossification (HO) is common following total hip arthroplasty (THA), the etiology of severe HO remains unclear. Herein, we describe a rare case of extremely severe HO after a PJI associated with a Staphylococcus caprae infection in a 78-year-old male patient. The patient had poorly controlled diabetes mellitus with no diabetic complications. The patient had no previous history of hip surgery, hip injury, or systemic bacterial infection. Immediately after the initial THA, he developed intermittent low-grade fever (37°C), which persisted for 3 months; consequently, he also reported mild hip pain during walking. He experienced a gradual decrease in hip range of motion within 5 years after the surgery, with progressive gait impairment. Two revision surgeries were required for the successful treatment of this difficult case. The patient's hip function improved, and the PJI was controlled following the second revision surgery. Based on the clinical course, CNS-caused PJI may lead to severe HO. This possibility warrants verification from an accumulated number of cases.

11.
Laser Ther ; 29(1): 53-60, 2020 Jul 17.
Article in English | MEDLINE | ID: mdl-32904059

ABSTRACT

BACKGROUND AND AIMS: Rejuvenation therapy using picosecond pulse laser and picosecond pulsed fractional therapy with a fractional lens have been performed with clinical effects evaluated. However, no histological analysis of effects on photoaged skin exists. In this study, influence of laser-toning and fractional therapy using picosecond pulse laser on photoaging was histologically investigated. SUBJECTS AND METHODS: The flexor side forearm of a male, age 61, with photoaging was divided into three 20 cm2 areas and irradiated with approximately 400 shots of 10-Hz laser, 8 mm spot size, and nine passes at an output of 0.7, 0.9, and 1.1 J/cm2 using picosecond laser-toning therapy six times, every two weeks. Two weeks post final irradiation, 2 mm punch biopsies were taken from the irradiation fields. Fractional therapy using Micro Lens Array (MLA) attached picosecond fractional therapy was applied to the medial crural skin with marked photoaging of a male, age 63. Irradiation was applied at 0.5 and 0.7 J/cm2 through two passes, with 3 mm punch biopsies taken from each irradiation field immediately after and again two months post-irradiation. Samples were subjected to hematoxylin and eosin (HE) and Elastica van Gieson staining and compared. RESULTS: In the picosecond laser-toning therapy sample, photoaging-induced dermis reconstruction occurred. The picosecond fractional therapy sample showed both epidermis and dermis reconstruction, with intrinsic aging and photoaging improvements. CONCLUSIONS: Recovery of dermal and epidermal age related atrophy by picosecond laser-toning and picosecond fractional therapy was histologically confirmed. Picosecond fractional therapy demonstrated superior improvement.

12.
Proc Natl Acad Sci U S A ; 117(11): 6178-6188, 2020 03 17.
Article in English | MEDLINE | ID: mdl-32123108

ABSTRACT

The nervous system evaluates environmental cues and adjusts motor output to ensure navigation toward a preferred environment. The nematode Caenorhabditis elegans navigates in the thermal environment and migrates toward its cultivation temperature by moving up or down thermal gradients depending not only on absolute temperature but on relative difference between current and previously experienced cultivation temperature. Although previous studies showed that such thermal context-dependent opposing migration is mediated by bias in frequency and direction of reorientation behavior, the complete neural pathways-from sensory to motor neurons-and their circuit logics underlying the opposing behavioral bias remain elusive. By conducting comprehensive cell ablation, high-resolution behavioral analyses, and computational modeling, we identified multiple neural pathways regulating behavioral components important for thermotaxis, and demonstrate that distinct sets of neurons are required for opposing bias of even single behavioral components. Furthermore, our imaging analyses show that the context-dependent operation is evident in sensory neurons, very early in the neural pathway, and manifested by bidirectional responses of a first-layer interneuron AIB under different thermal contexts. Our results suggest that the contextual differences are encoded among sensory neurons and a first-layer interneuron, processed among different downstream neurons, and lead to the flexible execution of context-dependent behavior.


Subject(s)
Behavior, Animal/physiology , Caenorhabditis elegans/physiology , Interneurons/physiology , Spatial Navigation/physiology , Thermoreceptors/physiology , Animals , Behavior Observation Techniques , Locomotion/physiology , Neural Pathways/physiology , Temperature , Thermosensing/physiology
13.
Proc Natl Acad Sci U S A ; 117(3): 1638-1647, 2020 01 21.
Article in English | MEDLINE | ID: mdl-31911469

ABSTRACT

Presynaptic plasticity is known to modulate the strength of synaptic transmission. However, it remains unknown whether regulation in presynaptic neurons can evoke excitatory and inhibitory postsynaptic responses. We report here that the Caenorhabditis elegans homologs of MAST kinase, Stomatin, and Diacylglycerol kinase act in a thermosensory neuron to elicit in its postsynaptic neuron an excitatory or inhibitory response that correlates with the valence of thermal stimuli. By monitoring neural activity of the valence-coding interneuron in freely behaving animals, we show that the alteration between excitatory and inhibitory responses of the interneuron is mediated by controlling the balance of two opposing signals released from the presynaptic neuron. These alternative transmissions further generate opposing behavioral outputs necessary for the navigation on thermal gradients. Our findings suggest that valence-encoding interneuronal activity is determined by a presynaptic mechanism whereby MAST kinase, Stomatin, and Diacylglycerol kinase influence presynaptic outputs.


Subject(s)
Caenorhabditis elegans/metabolism , Neurons/physiology , Synaptic Transmission/physiology , Taxis Response/physiology , Animals , Behavior, Animal , Caenorhabditis elegans Proteins/metabolism , Diacylglycerol Kinase/metabolism , Glutamic Acid/metabolism , Interneurons/physiology , Microtubule-Associated Proteins/metabolism , Neuropeptides/metabolism
14.
Genes Cells ; 25(3): 154-164, 2020 Mar.
Article in English | MEDLINE | ID: mdl-31917862

ABSTRACT

Innexins in invertebrates are considered to play roles similar to those of connexins and pannexins in vertebrates. However, it remains poorly understood how innexins function in biological phenomena including their function in the nervous systems. Here, we identified inx-4, a member of the innexin family in C. elegans, by a forward screening of thermotaxis-defective mutants. The inx-4 mutants exhibited abnormal migration to a temperature slightly higher than the cultivation temperature, called mild thermophilic behavior. Rescue experiments revealed that INX-4 acts in the major thermosensory neuron AFD to regulate thermotaxis behavior. INX-4::GFP fusion protein localized exclusively along axons in AFD neurons. In addition, over-expression of INX-4 in AFD neurons induced a cryophilic behavior, which is opposite to inx-4 mutants. Our findings suggest that INX-4/Innexin in AFD may fine-tune the execution of thermotaxis behavior when moving to desired temperatures.


Subject(s)
Caenorhabditis elegans/metabolism , Temperature , Animals , Mutation
15.
Bone Joint J ; 101-B(11): 1459-1463, 2019 11.
Article in English | MEDLINE | ID: mdl-31674236

ABSTRACT

AIMS: Rotational acetabular osteotomy (RAO) is an effective joint-preserving surgical treatment for acetabular dysplasia. The purpose of this study was to investigate changes in muscle strength, gait speed, and clinical outcome in the operated hip after RAO over a one-year period using a standard protocol for rehabilitation. PATIENTS AND METHODS: A total of 57 patients underwent RAO for acetabular dysplasia. Changes in muscle strength of the operated hip, 10 m gait speed, Japanese Orthopaedic Association (JOA) hip score, and factors correlated with hip muscle strength after RAO were retrospectively analyzed. RESULTS: Three months postoperatively, the strength of the operated hip in flexion and abduction and gait speed had decreased from their preoperative levels. After six months, the strength of flexion and abduction had recovered to their preoperative level, as had gait speed. At one-year follow-up, significant improvements were seen in the strength of hip abduction and gait speed, but muscle strength in hip flexion remained at the preoperative level. The mean JOA score for hip function was 91.4 (51 to 100)) at one-year follow-up. Body mass index (BMI) showed a negative correlation with both strength of hip flexion (r = -0.4203) and abduction (r = -0.4589) one year after RAO. Although weak negative correlations were detected between strength of hip flexion one year after surgery and age (r = -0.2755) and centre-edge (CE) angle (r = -0.2989), no correlation was found between the strength of abduction and age and radiological evaluations of CE angle and acetabular roof obliquity (ARO). CONCLUSION: Hip muscle strength and gait speed had recovered to their preoperative levels six months after RAO. The clinical outcome at one year was excellent, although the strength of hip flexion did not improve to the same degree as that of hip abduction and gait speed. A higher BMI may result in poorer recovery of hip muscle strength after RAO. Radiologically, acetabular coverage did not affect the recovery of hip muscle strength at one year's follow-up. A more intensive rehabilitation programme may improve this. Cite this article: Bone Joint J 2019;101-B:1459-1463.


Subject(s)
Acetabulum/surgery , Hip Dislocation/physiopathology , Muscle Strength/physiology , Muscle, Skeletal/physiology , Osteotomy/methods , Adult , Female , Gait/physiology , Hip Dislocation/surgery , Hip Joint/physiology , Humans , Male , Middle Aged , Osteotomy/rehabilitation , Postoperative Care/methods , Retrospective Studies , Treatment Outcome , Walking Speed/physiology , Weight-Bearing/physiology , Young Adult
16.
Sci Rep ; 9(1): 10104, 2019 07 12.
Article in English | MEDLINE | ID: mdl-31300701

ABSTRACT

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive loss of motor neurons, for which there is no effective treatment. Previously, we generated a Caenorhabditis elegans model of ALS, in which the expression of dnc-1, the homologous gene of human dynactin-1, is knocked down (KD) specifically in motor neurons. This dnc-1 KD model showed progressive motor defects together with axonal and neuronal degeneration, as observed in ALS patients. In the present study, we established a behavior-based, automated, and quantitative drug screening system using this dnc-1 KD model together with Multi-Worm Tracker (MWT), and tested whether 38 candidate neuroprotective compounds could improve the mobility of the dnc-1 KD animals. We found that 12 compounds, including riluzole, which is an approved medication for ALS patients, ameliorated the phenotype of the dnc-1 KD animals. Nifedipine, a calcium channel blocker, most robustly ameliorated the motor deficits as well as axonal degeneration of dnc-1 KD animals. Nifedipine also ameliorated the motor defects of other motor neuronal degeneration models of C. elegans, including dnc-1 mutants and human TAR DNA-binding protein of 43 kDa overexpressing worms. Our results indicate that dnc-1 KD in C. elegans is a useful model for the screening of drugs against motor neuron degeneration, and that MWT is a powerful tool for the behavior-based screening of drugs.


Subject(s)
Amyotrophic Lateral Sclerosis/drug therapy , Drug Evaluation, Preclinical/methods , Neuroprotective Agents/pharmacology , Nifedipine/pharmacology , Riluzole/pharmacology , Amyotrophic Lateral Sclerosis/pathology , Animals , Caenorhabditis elegans/drug effects , Caenorhabditis elegans/genetics , Caenorhabditis elegans Proteins/genetics , Disease Models, Animal , Dynactin Complex/genetics , Humans , Motor Neurons/pathology
17.
Aging Cell ; 18(3): e12906, 2019 06.
Article in English | MEDLINE | ID: mdl-30773781

ABSTRACT

PDZ domain-containing proteins (PDZ proteins) act as scaffolds for protein-protein interactions and are crucial for a variety of signal transduction processes. However, the role of PDZ proteins in organismal lifespan and aging remains poorly understood. Here, we demonstrate that KIN-4, a PDZ domain-containing microtubule-associated serine-threonine (MAST) protein kinase, is a key longevity factor acting through binding PTEN phosphatase in Caenorhabditis elegans. Through a targeted genetic screen for PDZ proteins, we find that kin-4 is required for the long lifespan of daf-2/insulin/IGF-1 receptor mutants. We then show that neurons are crucial tissues for the longevity-promoting role of kin-4. We find that the PDZ domain of KIN-4 binds PTEN, a key factor for the longevity of daf-2 mutants. Moreover, the interaction between KIN-4 and PTEN is essential for the extended lifespan of daf-2 mutants. As many aspects of lifespan regulation in C. elegans are evolutionarily conserved, MAST family kinases may regulate aging and/or age-related diseases in mammals through their interaction with PTEN.


Subject(s)
Caenorhabditis elegans Proteins/metabolism , PTEN Phosphohydrolase/metabolism , Animals , Caenorhabditis elegans/genetics , Caenorhabditis elegans Proteins/genetics , Longevity/genetics , PDZ Domains/genetics , PTEN Phosphohydrolase/genetics
18.
Commun Biol ; 1: 123, 2018.
Article in English | MEDLINE | ID: mdl-30272003

ABSTRACT

Animals must modify their behavior with appropriate timing to respond to environmental changes. Yet, the molecular and neural mechanisms regulating the timing of behavioral transition remain largely unknown. By performing forward genetics to reveal mechanisms that underlie the plasticity of thermotaxis behavior in C. elegans, we demonstrated that SLO potassium channels and a cyclic nucleotide-gated channel, CNG-3, determine the timing of transition of temperature preference after a shift in cultivation temperature. We further revealed that SLO and CNG-3 channels act in thermosensory neurons and decelerate alteration in the responsiveness of these neurons, which occurs prior to the preference transition after a temperature shift. Our results suggest that regulation of sensory adaptation is a major determinant of latency before animals make decisions to change their behavior.

19.
J Orthop Sci ; 23(6): 967-972, 2018 Nov.
Article in English | MEDLINE | ID: mdl-30055877

ABSTRACT

BACKGROUND: The use of 3-dimensional highly porous acetabular cups is increasing. Their structure and mechanical properties mimic those of natural bone; therefore, they should promote stronger biological fixation. In our experience with total hip arthroplasty, radiolucent lines are observed when a 3-dimensional highly porous cup (Stryker Tritanium) is used. We compared the clinical and radiographic results between a Tritanium cup and a conventional cup (Stryker Trident HA) over a short time period. METHOD: We retrospectively compared consecutive cases of primary total hip arthroplasty using a Tritanium cup (130 cases in 118 patients) and a matched cohort using a Trident cap (130 cases in 130 patients) between January 2011 and December 2014. RESULTS: The mean follow-up duration was 41.3 and 38.1 months (p = 0.06) for the Tritanium and Trident groups, respectively. There were significant differences between the groups for radiolucent lines, cup abduction angle, and cup-center-edge angle. There were no significant differences in the clinical results. Radiolucent lines increased in the Tritanium group (36.1% at 3 months and 60.7% at final follow-up), whereas they decreased in the Trident group (2.5% at 3 months and 0.8% at final follow-up). The occurrence of radiolucent lines was significantly higher in the Tritanium group than in the Trident group at each follow-up period. Radiolucent lines were seen in 36.1% of patients in the Tritanium group during follow-up, without initial gaps. One cup loosening in the Tritanium group was identified at the final follow-up evaluation. CONCLUSION: Both groups showed successful clinical results over short-term follow-up; however, the Tritanium group had a significantly higher rate of radiolucent line occurrence around the cups than did the Trident group. Thus, radiolucent lines can occur when using highly porous titanium cups; these lines indicate the possibility of future cup loosening. Longer follow-up and assessment of the results of using this implant are necessary.


Subject(s)
Arthroplasty, Replacement, Hip/instrumentation , Durapatite , Hip Prosthesis , Osteoarthritis, Hip/surgery , Prosthesis Design , Titanium , Acetabulum , Adult , Aged , Aged, 80 and over , Female , Humans , Japan , Male , Middle Aged , Osteoarthritis, Hip/diagnostic imaging , Osteoarthritis, Hip/etiology , Porosity , Radiography , Retrospective Studies , Treatment Outcome
20.
PLoS Comput Biol ; 14(5): e1006122, 2018 05.
Article in English | MEDLINE | ID: mdl-29718905

ABSTRACT

Animals are able to reach a desired state in an environment by controlling various behavioral patterns. Identification of the behavioral strategy used for this control is important for understanding animals' decision-making and is fundamental to dissect information processing done by the nervous system. However, methods for quantifying such behavioral strategies have not been fully established. In this study, we developed an inverse reinforcement-learning (IRL) framework to identify an animal's behavioral strategy from behavioral time-series data. We applied this framework to C. elegans thermotactic behavior; after cultivation at a constant temperature with or without food, fed worms prefer, while starved worms avoid the cultivation temperature on a thermal gradient. Our IRL approach revealed that the fed worms used both the absolute temperature and its temporal derivative and that their behavior involved two strategies: directed migration (DM) and isothermal migration (IM). With DM, worms efficiently reached specific temperatures, which explains their thermotactic behavior when fed. With IM, worms moved along a constant temperature, which reflects isothermal tracking, well-observed in previous studies. In contrast to fed animals, starved worms escaped the cultivation temperature using only the absolute, but not the temporal derivative of temperature. We also investigated the neural basis underlying these strategies, by applying our method to thermosensory neuron-deficient worms. Thus, our IRL-based approach is useful in identifying animal strategies from behavioral time-series data and could be applied to a wide range of behavioral studies, including decision-making, in other organisms.


Subject(s)
Behavior, Animal/physiology , Caenorhabditis elegans/physiology , Decision Making/physiology , Learning/physiology , Reinforcement, Psychology , Taxis Response/physiology , Animals , Computational Biology
SELECTION OF CITATIONS
SEARCH DETAIL
...