“Round Up the Usual Suspects”: A Comment on Nonexistent Plant G Protein-Coupled Receptors

An evolutionary argument supports the conclusion that plants do not have G protein coupled receptors.In the classic 1942 movie Casablanca, Vichy Police Captain Louis Renault obfuscated the truth by commanding his lieutenants to “round up the usual suspects,” knowing well that the culprit with the gun stood in plain view. Something similar has happened in the plant G protein field. This Scientific Correspondence was written to shed light on the source of misunderstanding and to preempt further confusion. Plant heterotrimeric G proteins are self-activating and therefore do not need and do not utilize G protein-coupled receptors (GPCRs). This conclusion was reached previously from biochemical analyses of plant G proteins (Johnston et al., 2007a; Urano et al., 2012); here, we buttress this point of view using an evolutionary argument. Proteins suspected as plant GPCRs were “rounded up” because they have the predicted topology of animal GPCRs and/or have been misannotated as such; however, these proteins are highly conserved in organisms that lack heterotrimeric G proteins. Therefore, they have functions unrelated to G-coupled signaling. Instead, the culprit protein standing in plain view is a receptor GTPase-accelerating protein (GAP), a receptor GAP called AtRGS1 (for regulator of G signaling).     

THE REPAIR OF DIFFICULT INGUINAL HERNIAS—Resection of the Spermatic Cord

A method of removing the cord structures from the inguinal canal and preserving the testis and the portion of the spermatic cord distal to the external ring was used in repair of large or recurrent hernias in 14 patients. Only one patient had pronounced testicular atrophy. In one case there was recurrence through the femoral canal. The procedure is simpler and shorter than removal of the testicle as well as the cord.     

Cutaneous Photobiology. The Melanocyte vs. the Sun: Who Will Win the Final Round?

Solar ultraviolet radiation (UV) is a major environmental factor that dramatically alters the homeostasis of the skin as an organ by affecting the survival, proliferation and differentiation of various cutaneous cell types. The effects of UV on the skin include direct damage to DNA, apoptosis, growth arrest, and stimulation of melanogenesis. Long‐term effects of UV include photoaging and photocarcinogenesis. Epidermal melanocytes synthesize two main types of melanin: eumelanin and pheomelanin. Melanin, particularly eumelanin, represents the major photoprotective mechanism in the skin. Melanin limits the extent of UV penetration through the epidermal layers, and scavenges reactive oxygen radicals that may lead to oxidative DNA damage. The extent of UV‐induced DNA damage and the incidence of skin cancer are inversely correlated with total melanin content of the skin. Given the importance of the melanocyte in guarding against the adverse effects of UV and the fact that the melanocyte has a low self‐renewal capacity, it is critical to maintain its survival and genomic integrity in order to prevent malignant transformation to melanoma, the most fatal form of skin cancer. Melanocyte transformation to melanoma involves the activation of certain oncogenes and the inactivation of specific tumor suppressor genes. This review summarizes the current state of knowledge about the role of melanin and the melanocyte in photoprotection, the responses of melanocytes to UV, the signaling pathways that mediate the biological effects of UV on melanocytes, and the most common genetic alterations that lead to melanoma.     

TREATMENT OF INTRAORAL CARCINOMA—Combined Resection of the Jaw and Radical Dissection of the Neck

Intraoral carcinomas first occur as primary growths. From these sites they spread by the lymphatics to the regional nodes. In the past, treatment of these lesions has consisted of radiation therapy for the primary lesion, followed by radical neck dissection. The results of this treatment have not been satisfactory. On the other hand, for carcinoma elsewhere in the body the results of surgical extirpation of the primary lesion, of the intervening lymphatics and of the regional nodes at the same operation has given much better results.In the past few years an attempt has been made to improve the results of treatment of intraoral carcinoma by removal in continuity of the primary lesion, intervening lymphatics and regional nodes. The improvement in anesthesiology, electrolytes and fluid balance, blood replacement, and the development of the antibiotics, in conjunction with the realization that the cosmetic deformity is not as great as might be expected, has led to this development. In those centers where it has been possible to apply this principle of treatment to intraoral carcinoma the results have been very encouraging.     

Tonsillectomy and the Risk for Deep Neck Infection—A Nationwide Cohort Study

Background

Although the tonsils contribute to first line immunity against foreign pathogens in the upper aero-digestive tract, the association of tonsillectomy with the risk of deep neck infection remains unclear. The aim of this study was to assess the incidence rate and risk of deep neck infection among patients who had undergone a tonsillectomy.

Methods

This retrospective cohort study evaluated all patients who had undergone tonsillectomy between 2001 and 2009 as identified from the Taiwan National Health Insurance Research Database. For each post-tonsillectomy patient, 10 age-, sex-, and index date-matched controls without a history of tonsillectomy were randomly selected. Cox Proportional hazard model and propensity score model were performed to evaluate the association between tonsillectomy and deep neck infection after adjusting for demographic and clinical data.

Results

There were 34 (71.6 cases per 100,000 person-years) and 174 (36.6 cases per 100,000 person-years) patients that developed deep neck infection in the tonsillectomized and comparison cohorts, respectively. After adjusting for covariates, patients who had undergone a tonsillectomy had a 1.71-fold greater risk of deep neck infection by both Cox proportional hazard model (95% confidence interval, 1.13-2.59) and propensity score model (95% confidence interval, 1.10-2.66). This association was not altered regardless of the indication for tonsillectomy (i.e. chronic/recurrent tonsillitis or sleep apnea/hypertrophy of tonsil) (p = 0.9797).

Conclusions

Based on our review of a nationwide cohort study we identified that the risk of deep neck infection is significantly increased among patients who have undergone a tonsillectomy. Additional research is needed to explore the possible mechanisms behind these findings.     

Proteomic Analysis of PKCγ-Related Proteins in the Spinal Cord of Morphine-Tolerant Rats

Background

Morphine tolerance is a common drawback of chronic morphine exposure, hindering use of this drug. Studies have shown that PKCã may play a key role in the development of morphine tolerance, although the mechanisms are not fully known.

Methodology/Principal Findings

In a rat model of morphine tolerance, PKCã knockdown in the spinal cord was successfully carried out using RNA interference (RNAi) with lentiviral vector-mediated short hairpin RNA of PKCã (LV-shPKCã). Spinal cords (L4-L5) were obtained surgically from morphine-tolerant (MT) rats with and without PKCã knockdown, for comparative proteomic analysis. Total proteins from the spinal cords (L4-L5) were extracted and separated using two-dimensional gel electrophoresis (2DGE); 2D gel images were analyzed with PDQuest software. Seven differential gel-spots were observed with increased spot volume, and 18 spots observed with decreased spot volume. Among these, 13 differentially expressed proteins (DEPs) were identified with matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS), comparing between MT rats with and without PKCã knockdown. The DEPs identified have roles in the cytoskeleton, as neurotrophic factors, in oxidative stress, in ion metabolism, in cell signaling, and as chaperones. Three DEPs (GFAP, FSCN and GDNF) were validated with Western blot analysis, confirming the DEP data. Furthermore, using immunohistochemical analysis, we reveal for the first time that FSCN is involved in the development of morphine tolerance.

Conclusions/Significance

These data cast light on the proteins associated with the PKCã activity during morphine tolerance, and hence may contribute to clarification of the mechanisms by which PKCã influences MT.     

Simultaneous Brain–Cervical Cord fMRI Reveals Intrinsic Spinal Cord Plasticity during Motor Sequence Learning

The spinal cord participates in the execution of skilled movements by translating high-level cerebral motor representations into musculotopic commands. Yet, the extent to which motor skill acquisition relies on intrinsic spinal cord processes remains unknown. To date, attempts to address this question were limited by difficulties in separating spinal local effects from supraspinal influences through traditional electrophysiological and neuroimaging methods. Here, for the first time, we provide evidence for local learning-induced plasticity in intact human spinal cord through simultaneous functional magnetic resonance imaging of the brain and spinal cord during motor sequence learning. Specifically, we show learning-related modulation of activity in the C6–C8 spinal region, which is independent from that of related supraspinal sensorimotor structures. Moreover, a brain–spinal cord functional connectivity analysis demonstrates that the initial linear relationship between the spinal cord and sensorimotor cortex gradually fades away over the course of motor sequence learning, while the connectivity between spinal activity and cerebellum gains strength. These data suggest that the spinal cord not only constitutes an active functional component of the human motor learning network but also contributes distinctively from the brain to the learning process. The present findings open new avenues for rehabilitation of patients with spinal cord injuries, as they demonstrate that this part of the central nervous system is much more plastic than assumed before. Yet, the neurophysiological mechanisms underlying this intrinsic functional plasticity in the spinal cord warrant further investigations.