Startle reflex modulation during threat of shock and “threat” of reward

During threat of shock, the startle reflex is potentiated, suggesting modulation by defensive mobilization. To determine whether startle potentiation is specific to aversive anticipation, startle reflexes were measured in the context of either aversive or appetitive anticipation in a between‐subject study. Participants wore a device on the wrist that could deliver electrical shock (n = 49), or vibrotactile stimulation indicating monetary reward (n = 48). Cues signaling “threat” or “safe” periods were presented alone, or accompanied by presentation of affective and neutral pictures on half of the trials. Results indicated that the startle reflex was significantly potentiated when anticipating either shock or reward, compared to safe periods, both when no picture was presented, as well as during picture viewing. The difference between threat and safety in both reflex magnitude and skin conductance changes was larger for those anticipating shock, suggesting that the aversive context was more motivationally engaging. The pattern of reflex modulation as a function of picture valence varied under threat and safety, but was identical in the shock and reward groups, consistent with a hypothesis that anticipation of either aversive or appetitive events prompts heightened perceptual vigilance, potentiating the acoustic startle reflex.     

Differential motivational responses to food and pleasurable cues in anorexia and bulimia nervosa: a startle reflex paradigm

BACKGROUND: Abnormal perceptions of food and shape underpin the cognitive behavioural model of eating disorders (EDs). The aim of this study was to investigate motivational processing of disorder-specific and standard emotional cues in anorexia (AN) and bulimia nervosa (BN) using startle eyeblink modulation (SEM). SEM was used because it is sensitive to motivational states of approach (appetitive response) and withdrawal (aversive response), which are independent of conscious intentional control. METHOD: Acoustically elicited SEM and subjective anxiety ratings were measured in 30 female patients with an ED (n=15 AN, n=15 BN) and 30 female control subjects while they viewed ED-relevant stimuli (food, female bodies) and standardized emotional pictures. RESULTS: BN subjects showed an appetitive response (startle inhibition) to food relative to neutral cues that differed significantly from AN subjects. By contrast, self-reports indicated significantly increased anxiety related to food cues across both ED groups. To female body picture (relative to neutral) cues, no significant between-group differences were found for SEM. ED subjects unexpectedly showed an aversive response (startle potentiation) to positive cues, in contrast to controls, who showed the established startle attenuation. CONCLUSIONS: These preliminary results suggest that BN patients demonstrated an exaggerated appetitive response to food but not to standardized positive cues, whereas SEM in AN patients points to a generalized failure to activate the appetitive motivational system. Differences in motivational salience to food cues are in line with distinctions between AN and BN in eating behaviour and food consumption and support differential treatment requirements.     

Pavlovian aversive and appetitive odor conditioning in humans: subjective, peripheral, and electrocortical changes

The effects of presynaptic guanosine-5'-O-(3-thio)triphosphate (GTPγS) on GABAergic inhibitory postsynaptic currents (IPSCs) were studied in cultured hippocampal neurons using whole-cell recordings. Inclusion of GTPγS (0.5–1 mM) in the presynaptic electrode reduced both the amplitude and paired-pulse depression of IPSCs, indicating that the probability of GABA-release had been reduced. Presynaptic GTPγS increased the depression of IPSCs by the GABA_B-receptor-agonist baclofen (10 μM), and the effect of baclofen was poorly reversible after washing. Stimulation of the GABAergic neuron at 80 Hz for 1 s was accompanied by tetanic depression of the IPSCs by 52±6% and was followed by post-tetanic potentiation (PTP), reaching a peak value of 71±21% and lasting about 100 s. IPSCs evoked after tetanic stimulation were depressed and PTP was absent when tetanic stimulation was applied within 3 min after starting injection of GTPγS into the presynaptic neuron. At longer times, basal release underlying a single IPSC was depressed. This affected the ratios recorded in response to tetanic stimulations such that tetanic depression was abolished, while PTP increased to 117±34%. In conclusion, GTPγS reduces the probability of GABA-release in both a use- and time-dependent manner, most likely through an inhibitory action on presynaptic Ca²⁺-influx through voltage-gated Ca²⁺ channels or an interaction with small GTP-binding proteins in the nerve terminals. Electronic Publication     

“Hypotyrosinemia” in Phenylketonuria

It has been postulated that the significant incidence of learning disabilities in well-treated patients with phenylketonuria (PKU) may be due, in part, to reduced production of neurotransmitters as a result of deficient tyrosine transport across the neuronal cell membrane. Hypotyrosinemia has been reported in treated and untreated PKU but virtually no data are available. We decided to examine this in our patient population and to compare it with the published norms, patient data from our hospital clinical biochemical laboratory database, and a group of normal children and adolescents in a private pediatric practice. We found that the mean nonfasting plasma tyrosine in 99 classical PKU patients was 41.1 μmol/L, in 26 mild (atypical) PKU patients 53.3 μmol/L, and in 35 non-PKU mild hyperphenylalaninemia patients 66.6 μmol/L. This compared to nonfasting plasma tyrosine levels in 102 non-PKU subjects of 64.0 μmol/L in our hospital biochemistry database, 69.1 μmol/L in 58 volunteers in the private office practice, and 64–78.8 μmol/L in infants, children, and adolescents in the literature review. Our data support the previously undocumented statements in the literature that plasma tyrosine levels are low in PKU.     

Perceptions of the “anorexic voice”: A qualitative study of health care professionals

People with anorexia nervosa (AN) often report experiencing a highly critical inner voice (AV) focused on their eating, shape, and weight. There are promising preliminary findings for its role in the treatment of AN, and the support of staff is vital for the AV to be embedded in treatment, but their views remain unknown. The aims of this study were to undertake a qualitative exploration of the perceptions of the AV among health care professionals (HCPs) in specialist eating disorder services. A thematic analysis was applied to interviews with 15 HCPs, including nurses, therapists, psychiatrists, health care assistants, psychologists, and dietitians. Two overarching themes were identified: “The AV is a vehicle for increasing compassion” and “It's not a one‐size‐fits‐all.” The AV was seen as a means of developing and sustaining compassion, but participants noted that it does not resonate for all clients. All HCPs in this study believed that there was potential benefit in utilizing the AV in their work with people with AN, and it is likely that doing so would help to reduce burnout and frustration within clinical teams.     

“Fast” and “slow” skeleto-fusimotor innervation in cat tenuissimus spindles; a study with the glycogen-depletion method

The glycogen-depletion method was used to investigate the motor supply to tenuissimus with respect to the presence of fast β axons and to assess the total proportion of both fast and slow β-innervated spindles in this muscle. In a first series of 5 expts., groups of motor axons with conduction velocities higher than 85 m/s were repetitively stimulated so as to produce glycogen depletion in the muscle fibres they innervated. The whole muscle was then quick-frozen, serially cut, stained to demonstrate glycogen and examined for intrafusal glycogen depletion. Zones of glycogen depletion were found in 16 of the 46 examined spindles; they were most frequently located in the longest of the chain intrafusal muscle fibres. Since it is known that there are no purely fusimotor axons to tenuissimus with conduction velocities above 50 m/s, it was concluded that β axons are present among the fastest axons to this muscle. In a second series of 5 expts. as many motor axons as possible with conduction velocities above 60 m/s were stimulated. Zones of glycogen depletion were found in 19 of the 47 examined spindles. They affected chain fibres in about half of the instances and bag₂ fibres in the others. As this latter location is characteristic of slow dynamic β axons, it was concluded that both slow and fast β axons occur regularly in the motor supply to tenuissimus. β-innervation is present in at least 40% of tenuissimus spindles with almost no convergence of fast and slow β axons onto the same spindle.     

Fine structural differences in “fast” and “slow” muscle fibers of the crab

The muscle fibers in the accessory flexor muscle of the crab were examined with the electron microscope. The limiting membrane of the muscle fiber invaginates at many points to form an internal extrafibrillar membranous system between the muscle fibrils. Two types of muscle fiber were found. In one, the fibrils are well separated from each other by an extensive membranous system, the sarcomere lengths are short, and the filaments in the A band are thick. This muscle fiber is the same as the fast fiber previously found physiologically. The other type of muscle fiber has large fibrils poorly separated by a relatively scant system of internal membranes. It has relatively long sarcomeres and comparatively thin filaments in the A band. This type of fiber is the same as the slow fibers described physiologically. Fibers intermediate in type are also found. Nerve terminals with typical synaptic vesicles occur and appear similar on both types of muscle fiber under the electron microscope. Membrane thickenings of nerve ending and muscle fiber also occur at the terminals on both types of muscle fiber. The nerve terminals on the fast fiber are much more easily found and hence more numerous than on the slow fiber. A comparison is made between the invertebrate and vertebrate fast and slow fibers, and some physiological implications of these findings are discussed.     

“WE'VE GOT A GUN?”: comparing reports of adolescents and their parents about household firearms

Firearms are a leading cause of mortality among adolescents, and the guns that adolescents use to harm themselves or others often come from their own homes. In this statewide, multilanguage, community‐based survey of 5,704 coresiding pairs of adolescents and their parents, we asked about guns in the home and compared their responses. The proportions of parents and adolescents responding affirmatively were similar: 25.7% and 26.8%, respectively, for any guns; 15.0% and 13.2%, respectively, for handguns. A paired analysis documented substantial agreement for whether there was any gun in the home and less agreement about whether there was a handgun in the home. The amount of agreement and disagreement was related to household composition and gender of the respondents. The disagreement was substantial for some groups (e.g., when boys residing in households containing a single mother and no other adults reported that there was a gun in the home, 64.8% of their mothers said that there was not a gun in the home). Implications for research and intervention are discussed. © 2007 Wiley Periodicals, Inc.     

“Giving” and “responding” differences in gestural communication between nonhuman great ape mothers and infants

In the first comparative analysis of its kind, we investigated gesture behavior and response patterns in 25 captive ape mother–infant dyads (six bonobos, eight chimpanzees, three gorillas, and eight orangutans). We examined (i) how frequently mothers and infants gestured to each other and to other group members; and (ii) to what extent infants and mothers responded to the gestural attempts of others. Our findings confirmed the hypothesis that bonobo mothers were more proactive in their gesturing to their infants than the other species. Yet mothers (from all four species) often did not respond to the gestures of their infants and other group members. In contrast, infants “pervasively” responded to gestures they received from their mothers and other group members. We propose that infants’ pervasive responsiveness rather than the quality of mother investment and her responsiveness may be crucial to communication development in nonhuman great apes.

     

“IH8U”: Confronting Cyberbullying and Exploring the Use of Cybertools in Teen Dating Relationships

Cyberbullying among adolescents has been a major focus of attention in mainstream media and has been documented to have many negative effects, as evidenced by several highly publicized suicides of teens who had been bullied online. The growing body of research about cyberbullying has rarely considered, however, the practice of cyberbullying between intimate partners. This article focuses on the frequency, types, and effect of cyberbullying between intimate partners in teen dating relationships. I examine the use of cybertools (electronic forms of communication) as mechanisms of power and control in relationships for both the target and the perpetrator. Suggested methods of prevention and intervention for adults working with teens who are experiencing cyberbullying in dating relationships are discussed.     

“Low-risk” and “High-risk” HPV-infection and K-ras Gene Point Mutations in Human Cervical Cancer: A Study of 31 Cases

To analyze the coexistence of human papilloma virus (HPV) infection and K-ras gene activation in cervical neoplasia, we investigated 31 (seven pre-invasive and 24 invasive) cervical carcinomas for “low-risk” (types 6 and 11) and “high-risk” (types 16 and 18) HPVs and K-ras point mutations using PCR-based technology. “Low-risk” HPVs were not detected in the group investigated; however, 20 of 31 (64%) cases were HPV 16 positive, while HPV 18 was found in only three (9.7%) samples (HPV 6/11 v. HPV 16/18, p < 0.0001; HPV 16 v. HPV 18, p < 0.0001; Fisher's exact test). There was a K-ras codon 12 point mutation in two of 31 (6.4%) neoplasms, with none of the cases showing a K-ras codon 13 point mutation. Two moderately differentiated squamous carcinomas showed K-ras exon 2 gene alterations. Interestingly, none of the pre-invasive cervical carcinomas displayed K-ras gene point mutations. The mean patient age did not differ significantly in the number of HPV-positive and -negative cases. A coexistence of “high-risk” human papillomavirus DNA with K-ras gene alterations was observed in three of 31 (9.7%) neoplasms (one IIA and two IB moderately differentiated cervical carcinomas). Our results suggest that “high-risk” HPVs coexist with K-ras gene alterations in a subset of moderately differentiated carcinomas of the cervix uteri.     

The Effects of “Immunosympathectomy” on Blood Pressure and Vascular “Reactivity” in Normal and Spontaneously Hypertensive Rats

Newborn litters of spontaneously hypertensive rats (SHR) and normotensive control rats (NCR) were identically treated with sympathetic nerve growth factor antiserum (Wellcome) which markedly interferes with adrenergic cardiovascular control (Zaimis 1967). Blood pressure, measured intermittently during 8 months, was in treated SHR (SHR_is) about 25 % higher than in NCR_is, their respective pressures being about 40 % and 25 % lower than those of sham-treated SHR and NCR.–The hindquarters of one SHR_is, or NCR_is, were then perfused at constant flow in parallel with those of ordinary NCR. Starting from maximal vasodilatation, resistance increases were induced by graded noradrenaline (NA) infusions, from “threshold” to maximal pressor responses. Compared to NCR_is, SHR_is showed an increased resistance at maximal dilatation, an increased slope of the NA dose-response curve and an increased maximal pressor response, while their NA “thresholds” did not differ significantly. Thus, the structurally determined hemodynamic differences between ordinary SHR and NCR (Folkow et al. 1970 b) characterize also SHR_is and NCR_is, though to a reduced extent. Even when comparing SHR_is with ordinary- NCR, which exhibited similar “resting” pressures, these differences partly remain, suggesting that the SHR resistance vessels might, for genetic reasons, be more prone to adapt structurally to pressure loads than those of NCR.     

Polymers by “criss-cross”-cycloaddition, 7. Segmented block copolymers

“Criss-cross”-cycloaddition of 4,4′-diisocyanatodiphenyl ether and 4-methoxybenzaldazine was used to synthesize α,ω-diisocyanato telechelics of molecular weights between 1 600 and 3 900. These precursors were reacted with different α,ω-dihydroxy functionalized aliphatic polyethers to produce segmented block copolymers in which the precursors obtained by cycloaddition reaction provide hard segment domains embedded in a polyether soft segment matrix. The resulting materials were soluble in common organic solvents such as tetrahydrofuran and chloroform and were characterized by spectroscopic techniques (¹H-, ¹³C NMR, IR spectroscopy) as well as gel permeation chromatography (GPC) for molar mass determination. The block copolymers were molded in a hot stage press, and the resulting samples were characterized by differential scanning calorimetry (DSC), dynamic mechanical thermal analysis (DMTA) and stress-strain measurement. The materials with a hard segment fraction below 0.36 and a molecular weight above M?_n = 90 000 were elastomers with ultimate elongations above 700%.     

Structural analysis of the components of Chinese lacquer “Kuro-urushi”

The urushiol components in Chinese lacquer “Kuro-urushi”, which was processed by treating Chinese Raw Urushi (“Ki-urushi”) with Fe(OH)₂, were isolated by reversed-phase liquid chromatography. A new component, which was not present in “Ki-urushi”, was found. Structural analysis using ¹H NMR and mass spectrometry showed that the component is a regioselectively formed water adduct of the original urushiol component, i. e., 3-(11′E,13′Z-8′-hydroxypentadecadienyl)catechol.     

Bone “mass” and the “mechanostat”: A proposal

The observed fit of bone mass to a healthy animal's typical mechanical usage indicates some mechanism or mechanisms monitor that usage and control the three longitudinal growth, bone modeling, and BMU-based remodeling activities that directly determine bone mass. That mechanism could be named a mechanostat. Accumulated evidence suggests it includes the bone itself, plus mechanisms that transform its mechanical usage into appropriate signals, plus other mechanisms that detect those signals and then direct the above three biologic activities. In vivo studies have shown that bone strains in or above the 1500–3000 microstrain range cause bone modelling to increase cortical bone mass, while strains below the 100–300 microstrain range release BMU-based remodeling which then removes existing cortical-endosteal and trabecular bone. That arrangement provides a dual system in which bone modeling would adapt bone mass to gross overloading, while BMU-based remodeling would adapt bone mass to gross underloading, and the above strain ranges would be the approximate “setpoints” of those responses. The anatomical distribution of those mechanical usage effects are well known. If circulating agents or disease changed the effective setpoints of those responses their bone mass effects should copy the anatomical distribution of the mechanical usage effects. That seems to be the case for many agents and diseases, and several examples are discussed, including postmenopausal osteoporosis, fluoride effects, bone loss in orbit, and osteogenesis imperfecta. The mechanostat proposal is a seminal idea which fits diverse evidence but it requires critique and experimental study.     

“Conservations” with a chimpanzee

Two chimpanzees (Pan tryglodytes), Fanny and Jane, were presented with liquid and number conservation problems. One chimpanzee, Jane, was successful in solving both sets of problems in that she was not distracted by irrelevant transformations, being influenced only by changes in quantity. Her success appeared to be based on the ability to make inferences rather than on simple perceptual judgement of the final comparison. The results are compared and contrasted with those of Premack, in G. Woodruff, D. Premack, and K. Kennel [(1978). Conservation of liquid and solid quantity by the chimpanzee. Science, 202:99–994] and J. Mehler and T. G. Bever [(1967). Cognitive capacity of very young children. Science, 158:141–142; (1968). Quantification, conservation and nativism. Science, 162:979–981], and it is suggested that there may be a similarity of conservation development between chimpanzees and man.     

“Living” free radical ring‐opening polymerization of 2‐methylene‐4‐phenyl‐1,3‐dioxolane by atom transfer radical polymerization

The “living” free radical ring‐opening polymerization of 2‐methylene‐4‐phenyl‐1,3‐dioxolane (MPDO) in the presence of ethyl α‐bromobutyrate/CuBr/2,2′‐bipyridine at various temperatures has been investigated. In comparison with the conventional ring‐opening polymerization of MPDO, a lower content of ring‐opened unit in the polymer was found. The results of ln[M]₀/[M]) against polymerization time, (M_n)_th and (M_n)_NMR vs conversion, and GPC of the polymers are strongly indicative of the “living” polymerization process. Initiator efficiency was measured. The mechanism of polymerization, and the effect of pyridine on the polymerization mechanism were discussed.     

Fractional dissolution of “solid” unsubstituted cellulose

Activated cellulose (Solucell, DP_w = 1 400) was extracted stepwise at room temperatures by means of mixed solvents consisting of N,N‐dimethylacetamide (DMAc) and LiCl, starting with a salt concentration of 1 wt.‐% and increasing it in increments of 1 wt.‐% up to 7 wt.‐%. Upon the regeneration of the thus obtained cellulose fractions by pouring the solutions dropwise into a large surplus of water, part of the mixed solvent is occluded in the polymer. For that reason the cellulose samples were purified by redissolving them in Ni‐tren and by a second precipitation. This process, however, leads to pronounced polymer degradation. For that reason we have used a spinning nozzle to press the extracts in a highly dispersed form into water. Using this procedure the samples were no longer contaminated by inclusions. The intrinsic viscosities of the fractions (in an alkaline aqueous solution of ferric tartaric acid complex at 25°C) and their GPC diagrams (solvent DMAc + LiCl) demonstrate that the shortest chains ([η] = 208 mL/g) become soluble first and the longest chains ([η] = 680 mL/g) last. The present data lead to the following Kuhn‐Mark‐Houwink relation [η] = 4.13 DP_w^0.68. The current results indicate a promising route to obtain larger quantities of unsubstituted cellulose with narrow molecular weight distribution by means of suitable extraction strategies.     

Genomic analysis of “microphenotypes” in epilepsy

Large international consortia examining the genomic architecture of the epilepsies focus on large diagnostic subgroupings such as “all focal epilepsy” and “all genetic generalized epilepsy”. In addition, phenotypic data are generally entered into these large discovery databases in a unidirectional manner at one point in time only. However, there are many smaller phenotypic subgroupings in epilepsy, many of which may have unique genomic risk factors. Such a subgrouping or “microphenotype” may be defined as an uncommon or rare phenotype that is well recognized by epileptologists and the epilepsy community, and which may or may not be formally recognized within the International League Against Epilepsy classification system. Here we examine the genetic structure of a number of such microphenotypes and report in particular on two interesting clinical phenotypes, Jeavons syndrome and pediatric status epilepticus. Although no single gene reached exome-wide statistical significance to be associated with any of the diagnostic categories, we observe enrichment of rare damaging variants in established epilepsy genes among Landau–Kleffner patients (GRIN2A) and pediatric status epilepticus patients (MECP2, SCN1A, SCN2A, SCN8A).     

Block copolymers by transformation of living anionic polymerization into controlled/“living” atom transfer radical polymerization

A method for the transformation of living anionic polymerization (LAP) to controlled/“living” atom transfer radical polymerization (ATRP) is reported and utilized for the preparation of block copolymers. The macroinitiators, polystyrene and polystyrene-block-polyisoprene containing the 2-bromoisobutyryl end group (PS-Br, M_n = 12 200, M_w/M_n = 1.04; PS-b-PIP-Br, M_n = 16 800, M_w/M_n = 1.03), were prepared by LAP of styrene and styrene/isoprene, correspondingly, and suitable termination agents. These compounds were used as macroinitiators for controlled/“living” ATRP to prepare block copolymers with methyl acrylate (PS-b-PMA), butyl acrylate (PS-b-PBA), methyl methacrylate (PS-b-PMMA), a mixture of styrene and acrylonitrile (PS-b-P(S-r-AN)) and also chain extension with styrene (PS-b-PS and PS-b-PIP-b-PS). The block copolymers were characterized by means of size exclusion chromatography, ¹H NMR and FT-IR spectroscopy.