Symbiont-Mediated Host-Parasite Dynamics in a Fungus-Gardening Ant.

Group-living can promote the evolution of adaptive strategies to prevent and control disease. Fungus-gardening ants must cope with two sets of pathogens, those that afflict the ants themselves and those of their symbiotic fungal gardens. While much research has demonstrated the impact of specialized fungal pathogens that infect ant fungus gardens, most of these studies focused on the so-called higher attine ants, which are thought to coevolve diffusely with two clades of leucocoprinaceous fungi. Relatively few studies have addressed disease ecology of lower Attini, which are thought to occasionally recruit (domesticate) novel leucocoprinaceous fungi from free-living populations; coevolution between lower-attine ants and their fungi is therefore likely weaker (or even absent) than in the higher Attini, which generally have many derived modifications. Toward understanding the disease ecology of lower-attine ants, this study (a) describes the diversity in the microfungal genus Escovopsis that naturally infect fungus gardens of the lower-attine ant Mycocepurus smithii and (b) experimentally determines the relative contributions of Escovopsis strain (a possible garden disease), M. smithii ant genotype, and fungal cultivar lineage to disease susceptibility and colony fitness. In controlled in-vivo infection laboratory experiments, we demonstrate that the susceptibility to Escovopsis infection was an outcome of ant-cultivar-Escovopsis interaction, rather than solely due to ant genotype or fungal cultivar lineage. The role of complex ant-cultivar-Escovopsis interactions suggests that switching M. smithii farmers onto novel fungus types might be a strategy to generate novel ant-fungus combinations resistant to most, but perhaps not all, Escovopsis strains circulating in a local population of this and other lower-attine ants.

Safety and Outcomes in 100 Consecutive Donation After Circulatory Death Liver Transplants Using a Protocol That Includes Thrombolytic Therapy.

Donation after circulatory death (DCD) liver transplantation (LT) reportedly yields inferior survival and increased complication rates compared with donation after brain death (DBD). We compare 100 consecutive DCD LT using a protocol that includes thrombolytic therapy (late DCD group) to an historical DCD group (early DCD group n = 38) and a cohort of DBD LT recipients (DBD group n = 435). Late DCD LT recipients had better 1- and 3-year graft survival rates than early DCD LT recipients (92% vs. 76.3%, p = 0.03 and 91.4% vs. 73.7%, p = 0.01). Late DCD graft survival rates were comparable to those of the DBD group (92% vs. 93.3%, p = 0.24 and 91.4% vs. 88.2%, p = 0.62). Re-transplantation occurred in 18.4% versus 1% for the early and late DCD groups, respectively (p = 0.001). Patient survival was similar in all three groups. Ischemic-type biliary lesions (ITBL) occurred in 5%, 3%, and 0.2% for early DCD, late DCD, and DBD groups, respectively, but unlike in the early DCD group, in the late DCD group ITBL was endoscopically managed and resolved in each case. Using a protocol that includes a thrombolytic therapy, DCD LT yielded patient and graft survival rates comparable to DBD LT.

Liver transplantation for "very early" intrahepatic cholangiocarcinoma: International retrospective study supporting a prospective assessment.

UNLABELLED: The presence of an intrahepatic cholangiocarcinoma (iCCA) in a cirrhotic liver is a contraindication for liver transplantation in most centers worldwide. Recent investigations have shown that "very early" iCCA (single tumors ≤2 cm) may have acceptable results after liver transplantation. This study further evaluates this finding in a larger international multicenter cohort. The study group was composed of those patients who were transplanted for hepatocellular carcinoma or decompensated cirrhosis and found to have an iCCA at explant pathology. Patients were divided into those with "very early" iCCA and those with "advanced" disease (single tumor >2 cm or multifocal disease). Between January 2000 and December 2013, 81 patients were found to have an iCCA at explant; 33 had separate nodules of iCCA and hepatocellular carcinoma, and 48 had only iCCA (study group). Within the study group, 15/48 (31%) constituted the "very early" iCCA group and 33/48 (69%) the "advanced" group. There were no significant differences between groups in preoperative characteristics. At explant, the median size of the largest tumor was larger in the "advanced" group (3.1 [2.5-4.4] versus 1.6 [1.5-1.8]). After a median follow-up of 35 (13.5-76.4) months, the 1-year, 3-year, and 5-year cumulative risks of recurrence were, respectively, 7%, 18%, and 18% in the very early iCCA group versus 30%, 47%, and 61% in the advanced iCCA group, P = 0.01. The 1-year, 3-year, and 5-year actuarial survival rates were, respectively, 93%, 84%, and 65% in the very early iCCA group versus 79%, 50%, and 45% in the advanced iCCA group, P = 0.02. CONCLUSION: Patients with cirrhosis and very early iCCA may become candidates for liver transplantation; a prospective multicenter clinical trial is needed to further confirm these results. (Hepatology 2016;64:1178-1188).

Ant-fungus species combinations engineer physiological activity of fungus gardens.

Fungus-gardening insects are among the most complex organisms because of their extensive co-evolutionary histories with obligate fungal symbionts and other microbes. Some fungus-gardening insect lineages share fungal symbionts with other members of their lineage and thus exhibit diffuse co-evolutionary relationships, while others exhibit little or no symbiont sharing, resulting in host-fungus fidelity. The mechanisms that maintain this symbiont fidelity are currently unknown. Prior work suggested that derived leaf-cutting ants in the genus Atta interact synergistically with leaf-cutter fungi (Attamyces) by exhibiting higher fungal growth rates and enzymatic activities than when growing a fungus from the sister-clade to Attamyces (so-called 'Trachymyces'), grown primarily by the non-leaf cutting Trachymyrmex ants that form, correspondingly, the sister-clade to leaf-cutting ants. To elucidate the enzymatic bases of host-fungus specialization in leaf-cutting ants, we conducted a reciprocal fungus-switch experiment between the ant Atta texana and the ant Trachymyrmex arizonensis and report measured enzymatic activities of switched and sham-switched fungus gardens to digest starch, pectin, xylan, cellulose and casein. Gardens exhibited higher amylase and pectinase activities when A. texana ants cultivated Attamyces compared with Trachymyces fungi, consistent with enzymatic specialization. In contrast, gardens showed comparable amylase and pectinase activities when T. arizonensis cultivated either fungal species. Although gardens of leaf-cutting ants are not known to be significant metabolizers of cellulose, T. arizonensis were able to maintain gardens with significant cellulase activity when growing either fungal species. In contrast to carbohydrate metabolism, protease activity was significantly higher in Attamyces than in Trachymyces, regardless of the ant host. Activity of some enzymes employed by this symbiosis therefore arises from complex interactions between the ant host and the fungal symbiont.

Sex at the margins: parthenogenesis vs. facultative and obligate sex in a Neotropical ant.

Geographic parthenogenesis is a distribution pattern, in which parthenogenetic populations tend to live in marginal habitats, at higher latitudes and altitudes and island-like habitats compared with the sexual forms. The facultatively parthenogenetic ant Platythyrea punctata is thought to exhibit this general pattern throughout its wide range in Central America and the Caribbean Islands. Workers of P. punctata from the Caribbean produce diploid female offspring from unfertilized eggs by thelytokous parthenogenesis, and mated females and males are rare. In contrast, workers in one colony from Costa Rica were incapable of thelytoky; instead mated workers produced all female offspring. Because sample sizes were very low in former studies, we here use microsatellite markers and explicit tests of thelytoky to examine the population genetic structure of ancestral and derived populations of P. punctata throughout the Caribbean and Central America. Populations from the Caribbean islands were fully capable of parthenogenesis, and population genetic signatures indicate that this is the predominant mode of reproduction, although males are occasionally produced. In contrast, the northernmost population on the mainland (Texas) showed signatures of sexual reproduction, and individuals were incapable of reproduction by thelytoky. Contrary to expectations from a geographic parthenogenesis distribution pattern, most parts of the mainland populations were found to be facultatively thelytokous, with population genetic signatures of both sexual and parthenogenetic reproduction.

Segmental uniparental isodisomy on 5q32-qter in a patient with childhood-onset schizophrenia.

Schizophrenia is a severe mental disorder affecting approximately 1% of the world's population. Although the aetiology of schizophrenia is complex and multifactorial, with estimated heritabilities as high as 80%, genetic factors are the most compelling. Childhood-onset schizophrenia (COS), defined as onset of schizophrenia before the age of 13 years, is a rare and malignant form of the illness that may have more salient genetic influence. The first known case of paternal segmental uniparental isodisomy (iUPD) on 5q32-qter in a patient with COS is described, which adds to the previously known high rates of chromosomal abnormalities reported in this sample. iUPD is a rare genetic condition in which the offspring receives two chromosomal homologues from one parent. Segmental UPD is defined as UPD on a portion of a chromosome with biparental inheritance seen in the rest of the homologous pair. Complications owing to this abnormality may arise from malfunctioning imprinted genes or homozygosity of recessive disease-causing mutations. This aberration became apparent during whole-genomic screening of a COS cohort and is of particular interest because 5q has been implicated in schizophrenia by several genomewide linkage studies and positive gene associations. This report, therefore, presents more evidence that schizophrenia susceptibility gene, or genes, may be found on distal 5q.

Intensity to force translation: a new effect of stimulus-response compatibility revealed by analysis of response time and electromyographic activity of a prime mover.

In reaction time studies of stimulus-response compatibility, emphasis has been placed on the influence of spatial stimulus-response relationships, but what seems to be essential for the emergence of an effect of stimulus-response compatibility is the existence of a conceptual match between stimulus and response variables. This notion was at the origin of the present study to assess the compatibility relationship between the intensity of a visual stimulus and the force of a voluntary muscle contraction. A stimulus-response compatibility effect was demonstrated. This effect was entirely due to premotoric processes.

The formulae-relating slopes, correlation coefficients and variance ratios used to determine stimulus- or movement-related neuronal activity.

When recording single neuron discharge in an animal during the performance of a conditioned task, the functional interpretation of any change in neuronal activity after the conditioned stimulus but before the conditioned task is difficult. So far, such changes have been described as either stimulus- or movement-related. One way of classifying these two types of response has been to use the slope and correlation coefficient between the response latency and the behavioural reaction time. We show that this method is poor and propose a more valid approach.

Activity of neurons in area 5 during a simple arm movement in monkeys before and after deafferentation of the trained limb.

Unit recordings were performed in the postcentral cortex and focused on area 5 of awake monkeys during the execution of a learned movement of the contralateral forearm so that the time relationship between the motor act and any modification of neuronal activity could be precisely correlated. Recordings were obtained from intact animals (561 neurons) and after deafferentation (C1-T7) of the trained limb (344 neurons). Of the movement-related neurons in normal animals, 243 cells were located in area 5 and these cells were divided into two populations. The first population (66% of movement-related neurons) presented modifications of activity after the onset of movement and receptive fields, often complex, were identifiable for these somaesthetic-like cells. No such neurons were found in the same cortical area after deafferentation. The second population (34% of movement-related neurons) presented modifications of activity related to movement but these changes occurred well before the onset of movement, up to 280 ms before. These cells were also characterized by an absence of sensory modulation and they represented the entire population of movement-related neurons recorded in area 5 after deafferentation (124 neurons). The first population appears to subserve a complex somaesthetic function. The second population is subject to purely central influences which, in part, may be due to corollary discharge or internal feedback. However, this population most likely represents a command apparatus for movement located 'upstream' to the motor cortex.

A statistical method for the estimation of neuronal response latency and its functional interpretation.

The functional role of many central nervous structures has been inferred from the temporal relationship of a neuronal response with the different sensory and motor events in an experimental design such as when an animal performs a trained movement in response to a conditioned stimulus. However, this kind of data analysis leads to problems in estimating the occurrence and latency of any neuronal response. We examine these problems and propose a novel technique of data analysis to estimate the point of change in a sequence of neuronal discharge. Furthermore, data can be tested to see whether the neuronal response is related to the conditioned stimulus or the motor act. The method can also be used in the simple situation of determining the latency of a neuronal response after a stimulus.

Activity of nigral dopaminergic neurons after lesion of the neostriatum in rats.

As shown by post-mortem analysis the major neuropathological trait of Huntington's chorea is a degeneration of the intrinsic neurons of the neostriatum (caudate nucleus and putamen). Such a situation can be reproduced by a destruction of the neostriatum by kainic acid. When injected into the caudate nucleus this excitatory amino acid destroys the intrinsic neurons of the neostriatum and spares fairly well the passing fibers. In the present work, we have chosen to examine the influence of neostriatal destruction on the activity of identified dopaminergic cells in the pars compacta of the substantia nigra. As a key element in the nigro-neostriato-nigral loop, this structure is a relevant site for observing the functional effects of neostriatal lesion. Our research hypothesis was based on the generally accepted view that the suppression of the important neostriato-nigral pathway and in particular the inhibitory GABAergic contingent, could generate a hyperactivity of nigral dopaminergic cells. One may therefore consider that the dopaminergic hyperactivity produces abnormal messages which can influence via several pathways the motoneurons, and which participates in the genesis of the hyperkinetic movements characteristic of chorea. After destruction of the neostriatum, we have shown that the pattern of discharge of most identified nigral dopaminergic neurons becomes greatly disorganized. This drastic change in the pattern of activity cannot be interpreted as the simple 'lift of a brake' on these cells by the suppression of the inhibitory GABAergic striato-nigral tract.

Reorganization of area 5 neuron activity in trained deafferented monkeys.

A command function is attributable to certain area 5 neurons which clearly fire before movement in trained monkey. Statistical analysis allowed us to define two categories of spontaneous firing mode for these cells: type I which exhibits a random pattern of discharge (14%), and type II displaying markedly "bursty firing". After deafferentation, both categories were still observed in the same proportion. However, the discharge pattern and frequency in type II cells remained altered for 5 months. This paralleled rises in neural latency response (RS) and reaction time (RT). Beginning the 6th month, there was a progressive reorganization of the spontaneous activity along with normalization of RS and RT. Our results support the idea that an enhancement of the excitability of these area 5 neurons, initially depressed by the suppression of sensory inputs, occurs over time. This sensitivity gain could be due to neural network rearrangements induced by repetitive operant solicitation.

Instruction-related changes of neuronal activity in area 5 during a simple forearm movement in the monkey.

Unit recordings were made in area 5 of monkeys during the performance of a sound-triggered movement of the forearm. Changes in neuronal activity prior to the movement were observed in 188 neurons recorded in both normal and deafferented animals. When the discharge of these cells was analyzed as peristimulus histograms, it was seen that 152 neurons presented a pattern of discharge which was characterized by a brief modification in activity with a relatively constant latency after the auditory cue. Similar changes were observed in normal and deafferented animals but the latency was not the same for the two groups. These neurons may reflect the presence of a sensorimotor interface for the integration of instructions for movement and the subsequent genesis of motor commands.

Neuronal activity and information processing in motor control: from stages to continuous flow.

Some years ago, we proposed, along with others, that the isomorphism between models of information processing by stages and the organization of neural pathways connecting functionally specialized neuronal networks was a guideline for conducting experiments in which the integration of methods and concepts of cognitive psychology and of neurophysiology was a promising approach to increase our knowledge of the processes responsible for motor control. At a time when models of serially organized information processing stages are being increasingly challenged, the deciphering of the underlying brain processes increasingly suggests that current views about the linkage between neural structures and behavioural functions must be reconsidered. First, at the "molar" level, the notion of a functional specialization of neuronal networks as, for example, being "sensory", "sensorimotor" or "motor", has to be viewed as a quantitative and not as a qualitative concept. Second, at the "molecular" level, the notion of a clear-cut functional differentiation between neuronal units, or between small sets of neurons, must similarly be revised: a neuron may be more or less "sensory" or "motor" and, moreover, may share both these functional properties to varying degrees. When the brain processes responsible for movement control are reconsidered in the light of these two concepts--that is a functional heterogeneity of structurally defined neuronal networks, as well as a continuum in functional specification of isolated neuronal units--data collected by using single-cell recording of neuronal activity fit well into the model of a continuous flow of information processing: neural pathways from the cortical parietal association areas to the corticospinal apparatus appear as a privileged sensorimotor information stream along which the amount of neuronal activity responsible for movement planning progressively decreases, while the amount of neuronal activity involved in movement execution progressively increases.

Why does the single neuron activity change from trial to trial during sensory-motor task?

Single neuron activities from cortical areas of a monkey were recorded while performing a sensory-motor task (a choice reaction time task). Quantitative trial-by-trial analysis revealed that the timing of peak activity exhibited large variation from trial to trial, compared to the variation in the behavioral reaction time of the task. Therefore, we developed a multi-unit dynamic neural network model to investigate the effects of structure of neural connections on the variation of the timing of peak activity. Computer simulation of the model showed that, even though the units are connected in a cascade fashion, a wide variation exists in the timing of peak activity of neurons because of parallel organization of neural network within each unit.

A program for analysing single neuron activity by methods based on estimation of a change-point.

A program for analysing the sequences of discharge of a single neuron is presented. This program performs the following tasks: it tests if there is a neuronal response after a stimulus, it estimates the response latency and, in the case of an experiment with a conditioned movement, it estimates the onset of the movement and gives indications about the functional role of the neuron by analysing the variances of the stimulus-response and response-movement times. The methods used have been developed by the authors and are based on the estimation of a change point. The basic methods are published elsewhere but some novelties are presented here, in particular a robust estimator of a variance ratio.

Local nerve blocks for postoperative analgesia.

The effect of local nerve blockade on the relief of postoperative pain is reported in a series of 167 patients who underwent surgery of the arm, knee or foot. In 80% of cases analgesics were not required within 4 hours postoperatively, and in 39% analgesics were not required within 8 hours. Conventional methods of postoperative pain relief are not always effective. Local nerve blockade can be used to provide complete analgesia after limb surgery and is therefore of great value to postoperative care.

The challenges of change for learning disabilities nurses.

In the past ten years there have been many changes in care provision for people with learning disabilities. This article outlines the changes and discusses the impact they have had on the learning disability nurse's role.

How can autologous blood transfusions help our patients?

In modern day clinical nursing practice, respecting and encouraging patient autonomy, together with acting as advocate for the patient, is an integral part of holistic patient care. We have a 'duty of care' to our patients. So why, in the early days of the 21st century, are we still transfusing our patients with homologous blood products when there is a safer alternative which has been recognised for almost 200 years?