Complete Limbs Research Articles

First Valanginian (Early Cretaceous) ornithopod (Dinosauria, Ornithischia) from Patagonia

Here we describe a new ornithopod species, Emiliasaura alessandrii gen. et sp. nov. from Valanginian rocks (Early Cretaceous) of northwestern Patagonia. This new taxon exhibits affinities with the Rhabdodontomorpha and is primarily represented by two specimens of mid-sized ornithopods collected from different sites and stratigraphical levels of the Mulichinco Formation. The holotype specimen MLL-Pv-001 includes the coracoid, the proximal end of a scapula, a humerus and a complete right hind limb, whereas the paratype specimen MLL-Pv-006 preserves vertebral elements, haemal arches, an incomplete pelvis, and nearly complete hind limbs. The new taxon has an anteroposteriorly elongate ilium with a sigmoidal dorsal border and broad brevis shelf, a femur shaft with an extensive, mid-shaft positioned fourth trochanter, and a second pedal digit with a short, robust, blunt ungual phalanx similar to those in Ankylopollexia ornithopods. The new ornithopod taxon formed part of a diverse dinosaur association from the Mulichinco Fm that includes dicraeosaurid sauropods and carcharodontosaurid theropods, and represents the first South American record of a rhabdodontomorph, and the oldest and most primitive representative of this clade.

A new abelisaurid dinosaur from the end Cretaceous of Patagonia and evolutionary rates among the Ceratosauria.

Gondwanan dinosaur faunae during the 20 Myr preceding the Cretaceous-Palaeogene (K/Pg) extinction included several lineages that were absent or poorly represented in Laurasian landmasses. Among these, the South American fossil record contains diverse abelisaurids, arguably the most successful groups of carnivorous dinosaurs from Gondwana in the Cretaceous, reaching their highest diversity towards the end of this period. Here we describe Koleken inakayali gen. et sp. n., a new abelisaurid from the La Colonia Formation (Maastrichtian, Upper Cretaceous) of Patagonia. Koleken inakayali is known from several skull bones, an almost complete dorsal series, complete sacrum, several caudal vertebrae, pelvic girdle and almost complete hind limbs. The new abelisaurid shows a unique set of features in the skull and several anatomical differences from Carnotaurus sastrei (the only other abelisaurid known from the La Colonia Formation). Koleken inakayali is retrieved as a brachyrostran abelisaurid, clustered with other South American abelisaurids from the latest Cretaceous (Campanian-Maastrichtian), such as Aucasaurus, Niebla and Carnotaurus. Leveraging our phylogeny estimates, we explore rates of morphological evolution across ceratosaurian lineages, finding them to be particularly high for elaphrosaurine noasaurids and around the base of Abelisauridae, before the Early Cretaceous radiation of the latter clade. The Noasauridae and their sister clade show contrasting patterns of morphological evolution, with noasaurids undergoing an early phase of accelerated evolution of the axial and hind limb skeleton in the Jurassic, and the abelisaurids exhibiting sustained high rates of cranial evolution during the Early Cretaceous. These results provide much needed context for the evolutionary dynamics of ceratosaurian theropods, contributing to broader understanding of macroevolutionary patterns across dinosaurs.

An anencephalic heterophagus or parasitic twin

A case of 6-week-old female twins is presented. Twin 1 was fully formed, whereas twin 2 was parasitic, adhered to the left flank, and had anencephaly and complete upper limbs. Depending on the twins' overall condition, the recommendation is to separate conjoined twins as soon as possible for a better outcome.

Retinoic Acid-Induced Limb Duplications.

Retinoic acid (RA) and the family of molecules based on vitamin A known as retinoids have remarkable effects on limb regeneration in salamanders and newts and cause whole limb duplications in a concentration-dependent manner. They respecify all three axes of the limb-the proximodistal, the anteroposterior, and the dorsoventral axis. As a result, complete limbs can be induced to regenerate from distal amputation planes producing two limbs in tandem. Here, we describe the basic methods for undertaking these experiments as well as the use of new synthetic retinoids which have retinoic acid receptor-selective actions. These will be valuable tools in future studies on the molecular basis of limb duplications and thus our understanding of the nature of positional information in the regenerating salamander limb.

Genetic basis for an evolutionary shift from ancestral preaxial to postaxial limb polarity in non-urodele vertebrates

In most tetrapod vertebrates, limb skeletal progenitors condense with postaxial dominance. Posterior elements (such as ulna and fibula) appear prior to their anterior counterparts (radius and tibia), followed by digit-appearance order with continuing postaxial polarity. The only exceptions are urodele amphibians (salamanders), whose limb elements develop with preaxial polarity and who are also notable for their unique ability to regenerate complete limbs as adults. The mechanistic basis for this preaxial dominance has remained an enigma and has even been proposed to relate to the acquisition of novel genes involved in regeneration. However, recent fossil evidence suggests that preaxial polarity represents an ancestral rather than derived state. Here, we report that 5'Hoxd (Hoxd11-d13) gene deletion in mouse is atavistic and uncovers an underlying preaxial polarity in mammalian limb formation. We demonstrate this shift from postaxial to preaxial dominance in mouse results from excess Gli3 repressor (Gli3R) activity due to the loss of 5'Hoxd-Gli3 antagonism and is associated with cell-cycle changes promoting precocious cell-cycle exit in the anterior limb bud. We further show that Gli3 knockdown in axolotl results in a shift to postaxial dominant limb skeleton formation, as well as expanded paddle-shaped limb-bud morphology and ensuing polydactyly. Evolutionary changes in Gli3R activity level, which also played a key role in the fin-to-limb transition, appear to be fundamental to the shift from preaxial to postaxial polarity in formation of the tetrapod limb skeleton.

Multiple myeloma of young adult presented with paraplegia, rare case report in Saudi Arabia.

Multiple myeloma is the second most common hematologic malignancy. It is characterized by the neoplastic proliferation of plasma cells in the bone marrow, leading to excessive production of monoclonal immunoglobulin. The mean age at diagnosis is 65 years. There are only a few cases of Multiple Myeloma arising in young population reported in the literature. We present a case of 33-years-old male presented with complete bilateral lower limbs paralysis and loss of sensation which were gradual in onset and accompanied by upper and lower back pain for 1 month. MRI of the whole spine show multiple infiltrative bone marrow high signal in T2 and STIR sequences involve C4 and the upper dorsal vertebral bodies and the spinous process of D4 with left para-spinal and large posterior epidural mass compress the spinal cord. CT guidance obtains three samples from the mass and placed in formalin in separate containers. Histopathology examination revealed neoplastic growth composed of Sheet of diffuse atypical plasma cells infiltrating fibro collagenous and adipose tissue. Although Multiple myeloma is a disease of elderly; it still could present in young age group. Histopathology examination is the gold standard for diagnosis.

Peer-to-Peer Rounding to Reduce the Number of Peripheral Intravenous Infiltrations and Extravasations

Introduction: Early identification and quick response to an intravenous (IV) infiltrate are imperative to preventing harm. Peripheral IV (PIV) therapy is regarded as routine in hospitalized pediatric patients. IV infiltrate complications range from irritation and discomfort to serious harm, such as permanent skin and soft-tissue loss, impaired limb function, compartment syndrome, distal vascular compromise, and even loss of partial or complete limbs. A standardized intervention bundle to prevent harm was established at a Midwestern pediatric hospital as the standard of practice; however, bundle consistency and reliability were suboptimal despite communication and education through online and newsletter formats. Methods: Peer-to-peer rounding using a Kamishibai card was implemented to facilitate discussion between the bedside nurse and a PIV champion. The Kamishibai card consisted of questions for the champion to ask nurses to assess knowledge, application to practice, and give feedback to improve practice. Each month, 1 unit was selected for champions to round with nurses. Results: Rounding was well received by unit leadership and nurses. Maintenance bundle compliance was sustained >90% for 11 of 12 months in 2017 (Fig. 1). Approximately, 90 less children were harmed by moderate or severe infiltrates when comparing data from 2016 to 2017, which exceeded the target goal of a 20% reduction (Fig. 2).Fig. 1.: Peer-to-peer rounding began in November 2015 and continued throughout 2017 with marked improvement in maintenance bundle compliance over time.Fig. 2.: Percent of infiltrates by year: a 30% decrease in the number of moderate/severe infiltrates was noted between 2016 and 2017 with the utilization of a peer-to-peer rounding intervention.Conclusion: Targeted rounding by PIV champions engaged nurses in reducing harm and improving bundle reliability for pediatric patients with a PIV. Through peer-to-peer rounding, nurses heard consistent messages and had opportunities to discuss best practices and conquer barriers. ACKNOWLEDGMENTS The authors thank the peripheral intravenous champions for their hard work and perseverance in decreasing patient harm from peripheral IV infiltrations and extravasations.

Postcranial remains of Teraterpeton hrynewichorum (Reptilia: Archosauromorpha) and the mosaic evolution of the saurian postcranial skeleton

Teraterpeton hrynewichorum is an unusual archosauromorph reptile from the Upper Triassic (Carnian) Evangeline Member of the Wolfville Formation in Nova Scotia (Canada). Its long snout has transversely broad, cusped ‘molariform’ teeth posteriorly and lacks teeth anteriorly. The temporal region of the cranium is ‘euryapsid’ with large upper and closed lower temporal fenestrae. A previously undescribed specimen referable to Teraterpeton includes a nearly complete pelvic girdle and both hind limbs. The ilium has a long, dorsoventrally deep anterior process similar to that of derived rhynchosaurs. The pelvis has a well-developed thyroid fenestra, a feature shared only by Tanystropheidae among Archosauromorpha. Metatarsal V is proximodistally short, resembling the condition in Tanystropheidae. The pedal unguals of Teraterpeton are strongly flattened mediolaterally, dorsoventrally deep and weakly curved, much like the manual unguals. We performed a phylogenetic analysis of a matrix comprising 61 taxa of Permo-Triassic diapsid reptiles and 337 characters, which supports the position of Teraterpeton as the sister-taxon of Trilophosaurus + Spinosuchus. In the current phylogeny, parsimony-based character optimization of the aforementioned character-states in Teraterpeton indicate that all were acquired independently from other saurian lineages. The unusual combination of postcranial features in Teraterpeton underscores the critical importance of comprehensive taxon sampling for understanding the mode of character change among Triassic diapsid reptiles and careful apomorphy-based identifications to faunal analyses.

Exogenous Vitamin D signaling alters skeletal patterning, differentiation, and tissue integration during limb regeneration in the axolotl

Urodele amphibians such as the axolotl regenerate complete limbs as adults, and understanding how the “blueprint”, or pattern, of the regenerate is established and manipulated are areas of intense interest. Nutrient signaling plays an important role in pattern formation during regeneration. Retinoic acid signaling is the most characterized pathway during this process. Exogenous retinoic acid (RA) reprograms the pattern information in regenerating cells to a more posterior, ventral, and proximal identity. Vitamin D signaling shares several molecular similarities with RA and has been shown to alter pattern formation during zebrafish pectoral fin regeneration. To determine if exogenous Vitamin D signaling is capable of reprograming pattern in the axolotl limb blastema, we treated regenerating limbs with a potent Vitamin D agonist. Under the studied conditions, exogenous Vitamin D did not act in a manner similar to RA and failed to proximalize the pattern of the resulting regenerates. The Vitamin D treatment did result in several skeletal defects during regeneration, including carpal fusions along the A/P axis; failure to integrate the newly regenerated tissue with the existing tissue, formation of ectopic nodules of cartilage at the site of amputation, and altered bone morphology in uninjured skeletal tissue.

Animal carcass processing, cooking and consumption at Early Neolithic Revenia-Korinou, northern Greece

The open-air settlement of Revenia-Korinou has yielded the largest Early Neolithic (7th millennium BC) faunal assemblage to date from Greece. The assemblage, recovered from numerous pits, is heavily dominated by domestic sheep, goats, pigs and cattle. Here we focus on the evidence for butchery and consumption of animals, to explore how carcass products were cooked (in the absence of cooking pots) and what if any role they played in commensal politics. Evidence for dismembering and filleting is sparse, implying butchery of domestic animal carcasses into large segments (including more or less complete limbs) for cooking, apparently in ovens or pits rather than on open fires. Subsequently limb bones were intensively smashed to extract marrow and probably grease, perhaps by boiling in organic containers. Dismembering, filleting and marrow extraction were most intensive for cattle, but bone grease was more systematically exploited in the case of sheep/goats, implying differences between taxa in contexts of consumption. Significant differences between pits in taxonomic composition and the incidence of gnawing and burning suggest that each represents short-term and/or localized discard, perhaps by a small residential group. Within individual pits, matching unfused diaphyses and epiphyses and joins between fragments broken in antiquity confirm rapid burial, but bones separated by dismembering seem to have been dispersed across the settlement before discard. The distribution of carcass products, both cooked and uncooked, played a role in shaping relationships between small residential units and the wider community at Early Neolithic Revenia-Korinou.

Use of Cryodehydratated Animal Anatomical Segments for Veterinary Anatomy Teaching

Anatomical education in the Veterinary Schools around the world has been supported by diverse kinds of innovations such as digital resources and applications, being the use of cadaver’s dissections very limited. In the present study, the use of cryodehydrated anatomical pieces of musculoskeletal structures from large and small animals were experimented for five years and the vantages and advances were computed. The material was prepared using a fixation of fresh material with 10% formalin followed by dissections and freezed-unfreezed sequences until completely be dried. Paints were performed to give a natural appearance. The material produced, including complete limbs from large and small animals had a good quality and preservation of the structures such as ligaments, muscle mass, tends and aponeuroses. The topographical relationships were perfectly maintained and revealed to be a reliable material for the practices class of musculoskeletal anatomy. The method used was easy applied, very cheap, of stress-free manipulation and storage and due to its high durability reduced the discharge of biological wastes and chemical products. The students show very friendly to this kind of material what reflected in high coefficient of approval during the practical examinations. The experience of create additional assignment to teaching how to prepare the material was successful and have been a great integration opportunity to students from last years of the course work together and share experiences with the beginners, when they check anatomic contents considering the applicability in clinics and surgical assignments.

The axolotl limb blastema: cellular and molecular mechanisms driving blastema formation and limb regeneration in tetrapods.

The axolotl is one of the few tetrapods that are capable of regenerating complicated biological structures, such as complete limbs, throughout adulthood. Upon injury the axolotl generates a population of regeneration-competent limb progenitor cells known as the blastema, which will grow, establish pattern, and differentiate into the missing limb structures. In this review we focus on the crucial early events that occur during wound healing, the neural-epithelial interactions that drive the formation of the early blastema, and how these mechanisms differ from those of other species that have restricted regenerative potential, such as humans. We also discuss how the presence of cells from the different axes of the limb is required for the continued growth and establishment of pattern in the blastema as described in the polar coordinate model, and how this positional information is reprogrammed in blastema cells during regeneration. Multiple cell types from the mature limb stump contribute to the blastema at different stages of regeneration, and we discuss the contribution of these types to the regenerate with reference to whether they are "pattern-forming" or "pattern-following" cells. Lastly, we explain how an engineering approach will help resolve unanswered questions in limb regeneration, with the goal of translating these concepts to developing better human regenerative therapies.

A study on estimation of planar gait kinematics using minimal inertial measurement units and inverse kinematics.

This paper describes a preliminary study of using four inertial measurement units (IMUs) attached to the heel and pelvis to estimate the joint angles of normal subjects during walking. The IMU, consisting of a 3-D accelerometer and gyroscope, is used to estimate the planar displacement of the heel and pelvis and the angular change of heel in one gait cycle. We then model the gait as a planar 3R serial chain and solve its inverse kinematics by using such information. The results are validated by comparing the estimated joint angles of lower limbs (i.e. hip, knee and ankle angles) with an optical motion capture system. This study can benefit the future research on conducting complete lower limbs kinematics analysis with minimal and unobtrusive wearable sensors.

PRESERVATION POTENTIAL OF GECARCINID LAND CRABS (DECAPODA, BRACHYURA, GECARCINIDAE) FROM SAN SALVADOR

ABSTRACT Land crabs are found in marine and terrestrial sediments and sedimentary rocks from the Pleistocene and Holocene throughout the Caribbean. Field surveys of two widespread and abundant species, Gecarcinus lateralis and Gecarcinus ruricola, were conducted three times a week for 4 weeks along the northern coast of San Salvador Island, the Bahamas, at three localities that varied in vegetation cover, available sediment, and wind and wave energy. A total of 1400 identifiable remains were found and scored for four taphonomic characters: fragmentation, edge modification, surface alteration, and color loss. The majority of specimens exhibited various levels of disarticulation, from complete limbs to only isolated podomeres. Overall, claws are overrepresented, and the distribution of recovered remains differed significantly (p < 0.0001) from that expected based on the anatomy of a single crab (eight legs, two claws, and one carapace per individual). Remains found in direct sunlight and open spaces consist...

Position-specific induction of ectopic limbs in non-regenerating blastemas on axolotl forelimbs.

Ectopic retinoic acid (RA) has been hypothesized to reprogram the positional identity of cells in developing and regenerating limbs to a single positional value corresponding to the posterior‐ventral‐proximal (PVPr) position on the limb. We tested this hypothesis by using RA to reprogram the information of blastema cells that were induced to form at different positions around the limb circumference. We observed that RA treatment of blastemas in anterior and dorsal locations, but not posterior and ventral locations, resulted in the induction of complete ectopic limbs. These position‐specific differences in limb induction are probably due to differences in the positional disparity between the RA‐reprogrammed blastema cells and the cells at the periphery of the wound. These observations are consistent with the hypothesis that RA treatment reprograms the information in blastema cells to the PVPr position on the limb, since anterior and dorsal positions have the largest disparity and posterior and ventral have the smallest disparity from the PVPr identity.

A new specimen of theTriassic pistosauroidYunguisaurus, with implications for the origin ofPlesiosauria (Reptilia,Sauropterygia)

AbstractAn adult skeleton of the pistosauroid sauropterygianYunguisaurus liaereveals a number of morphological features not observed in the holotype, such as the complete morphology of the skull roof, stapes, atlas and axis, ventral view of the postcranium, and nearly complete limbs and tail. Size and morphological differences between the two specimens are mostly regarded as ontogenetic variation, and newly added data did not affect the phylogenetic relationships with other pistosauroids significantly. The number of mesopodia (11 carpals and 8 tarsals) exceeds that known in any otherTriassic marine reptiles and does not serve as a precursor of the plesiosaurian pattern with fewer mesopodia of different topology; it demonstrates variability of the limb morphology among theTriassic pistosauroids. The pectoral girdles ofCorosaurus,AugustasaurusandYunguisaurusmay indicate early stages of the adaptation towards the plesiosaurian style of paraxial limb movements with ventroposterior power stroke.

Morphology and composition of bone-bearing coprolites from the Late Permian Beaufort Group, Karoo Basin, South Africa

Bone-bearing coprolites are fossilised faeces of carnivores and as such they provide important information about food webs and feeding strategies of the ancient ecosystem. With this aim we examined the morphology and composition of Late Permian bone-bearing coprolites from the Hoedemaker Member of the Teekloof Formation (Lower Beaufort Group) of the southern Karoo Basin, South Africa. Analysis of the size and shape of 150 specimens collected from this member resulted in the recognition of 5 different morphotypes. Each morphotype is matched to carnivorous taxa within the Tropidostoma Assemblage Zone fauna which biostratigraphically defines the Hoedemaker Member strata in this part of the basin. Morphotype 1 are long cylinder-shaped non-segmented faeces, or possible cololites, rounded at both ends and commonly contain complete small bones as well as bone fragments and were most likely produced by the large gorgonopsians Aelurognathus and Gorgonops torvus. Smaller, tubular Morphotype 2 coprolites are attributed to the smaller therocephalians and juvenile gorgonopsians. Rare double-pointed Morphotype 3 are similar in size and shape to scats of the modern wild cat and we attribute these to the medium-sized gorgonopsians Cyonosaurus and Lycaenops or possibly juveniles of the large gorgonopsian species. Morphotype 4 coprolites are bullet-shaped and are interpreted as disaggregated portions of compound faeces. They are the most common coprolite found in the Hoedemaker mudrocks and are also attributed to small and medium-sized therocephalians and gorgonopsians. Morphotype 5 are rare flattened disc-shaped coprolites that contain abundant fish-scales and are linked to the temnospondyl, Rhinesuchus africanus, the only known piscivore from the Tropidostoma assemblage. Analyses of the microstructure of the bone inclusions within morphotypes 1–4 revealed two distinct tissue types. Bone tissue type A consists of highly vascularised, rapidly-forming bone interpreted as being that of very young perinatal and/or early juvenile therapsids, probably dicynodonts. Judging by the relative abundance of their body fossils, the herbivorous dicynodonts were by far the most abundant tetrapods in the Tropidostoma Assemblage Zone and it is probably that their young, both embryonic and neonatal juveniles, were commonly preyed upon. Some of the larger carnivores swallowed small prey whole, or with minimal mastication, allowing complete limbs to pass through the digestive tract in articulation. Inclusions of bone tissue type B, which consists of poorly-vascularised, slow-growing bone, are interpreted to be the skeletal remains of small parareptiles.

Applying Amphibian Limb Regeneration to Human Wound Healing

In contrast to the limited regenerative ability found in human wound healing, which often results in unsatisfying and deficient scar formation, urodele amphibians, with the Mexican axolotl as a prime example, expose an extraordinary regenerative capacity. This regeneration leads to a perfect restoration of tissue architecture, function, and aesthetics with the axolotl being actually able to reclaim complete limbs. Evolutionary considerations suggest that regeneration might be a biologic principle which also underlies human wound healing. Experimental findings, such as comparative studies on transforming growth factor-β and fibroblast growth factor accentuate this assumption. Regeneration, as recent data indicate, might be a question of adaptive immunity. The loss of regenerative potency correlates with the decrease of regeneration in most species, whereas the Mexican axolotl lacks adaptive immunity throughout its life. The characterization of molecular pathways as a prerequisite for any control of regenerative processes sets an increasing indication toward the transfer into human beings. Some regenerative techniques, eg, recombinant transforming growth factor-β have already emerged. Molecular findings suggest that there is an intrinsic regenerative capacity in humans which might be initiated under appropriate circumstances. The Mexican axolotl is liable to diverse surgical and molecular approaches. Though well-known among developmental biologists, its exploitation for experimental Plastic Surgery still has to be established. We therefore intend to give an introduction to amphibian regeneration and the common evolutionary roots of regeneration and human wound healing, as we believe that Plastic Surgery takes a unique advantage of performing basic research on amphibian regeneration.

Influence of lower limb rotation in navigated alignment analysis: implications for high tibial osteotomies

Inaccurate coronal plane realignment is a common problem after high tibial osteotomy. It has been shown that lower limb rotation has an effect on the two-dimensional measurement of lower limb alignment. Although alignment errors are known to occur due to limb rotation, the magnitude of this effect is unknown. Navigation systems allow for the measurements of coronal plane alignment and dynamically rotational and sagittal plane. Our study evaluated the effect of rotational leg movements on coronal plane alignment as determined by image-free navigation. We hypothesized that a linear relationship exists between rotation and angular measurements. Eight cadavers were used, while three test conditions of the complete lower limbs were established: (1) solid knee arthrodesis, (2) provisional knee arthrodesis and (3) unconstrained knee conditions. Navigated measurements of coronal and sagittal lower limb axis were done initially without knee flexion for defined internal/external rotations of 5 degrees, 10 degrees and maximal values for all test series. Repeated test for the unconstrained knee included stepwise knee flexion of 5 degrees, 10 degrees and 20 degrees. Statistical analysis comparing the test conditions 1, 2 and 3 and comparison between flexion movements of the unconstrained knee were done. Results revealed no significant differences between the different rotations of test condition 1 (mean 0.34 degrees, SD 0.23, range, 0 degrees-0.8 degrees). Condition 2 similarly did not result in significant deviations (mean 0.51 degrees, SD 0.24, range 0.1 degrees-0.9 degrees). Measurement deviations ranging from 0.4 degrees to 4.3 degrees were found for condition 3, the unconstrained knee. However, no statistically different testings from the arthrodesed knee were found (P=0.099-0.410). Knee flexion from 5 degrees, 10 degrees or 20 degrees, showed significant deviations (P<0.05) for all rotations at all degrees of flexion. Rotation and flexion of 5 degrees led to significant alignment errors of 3.4 degrees and 2.8 degrees, respectively, for internal and external rotations. Measurement failures due to the rotational movements of 1 degree-4 degrees might add to additional sources of errors causing relevant under- or over-corrections of the mechanical leg axis. Discrepancies of the axis due to rotational movements as well as flexion of the knee joint can be avoided and corrected immediately with the help of navigation.

Inhibition of Interferon-γ Signaling in Oligodendroglia Delays Coronavirus Clearance without Altering Demyelination

Infection of the central nervous system (CNS) by the neurotropic JHM strain of mouse hepatitis virus (JHMV) induces an acute encephalomyelitis associated with demyelination. To examine the anti-viral and/or regulatory role of interferon-γ (IFN-γ) signaling in the cell that synthesizes and maintains the myelin sheath, we analyzed JHMV pathogenesis in transgenic mice expressing a dominant-negative IFN-γ receptor on oligodendroglia. Defective IFN-γ signaling was associated with enhanced oligodendroglial tropism and delayed virus clearance. However, the CNS inflammatory cell composition and CD8+ T-cell effector functions were similar between transgenic and wild-type mice, supporting unimpaired peripheral and CNS immune responses in transgenic mice. Surprisingly, increased viral load in oligodendroglia did not affect the extent of myelin loss, the frequency of oligodendroglial apoptosis, or CNS recruitment of macrophages. These data demonstrate that IFN-γ receptor signaling is critical for the control of JHMV replication in oligodendroglia. In addition, the absence of a correlation between increased oligodendroglial infection and the extent of demyelination suggests a complex pathobiology of myelin loss in which infection of oligodendroglia is required but not sufficient.