Miracle-dz/UniFAR-FTUs huggingface dataset:
The anterior insula bidirectionally modulates cost‐benefit decision‐making on a rodent gambling task

Deficits in cost‐benefit decision‐making, as assessed in the Iowa Gambling Task (IGT), are commonly observed in neuropsychiatric disorders such as addiction. There is considerable variation in the maximization of rewards on such tasks, both in the general population and in rodent models, suggesting individual differences in decision‐making may represent a key endophenotype for vulnerability to neuropsychiatric disorders. Increasing evidence suggests that the insular cortex, which is involved in interoception and emotional processes in humans, may be a key neural locus in the control of decision‐making processes. However, the extent to which the insula contributes to individual differences in cost‐benefit decision‐making remains unknown. Using male Sprague Dawley rats, we first assessed individual differences in the performance over the course of a single session on a rodent analogue of the IGT (rGT). Rats were matched for their ability to maximize reward and received bilateral excitotoxic or sham lesions of the anterior insula cortex (AIC). Animals were subsequently challenged on a second rGT session with altered contingencies. Finally, animals were also assessed for instrumental conditioning and reversal learning. AIC lesions produced bidirectional alterations on rGT performance; rats that had performed optimally prior to surgery subsequently showed impairments, and animals that had performed poorly showed improvements in comparison with sham‐operated controls. These bidirectional effects were not attributable to alterations in behavioural flexibility or in motivation. These data suggest that the recruitment of the AIC during decision‐making may be state‐dependent and help guide response selection towards subjectively favourable options.
Efficient Presentation of House Dust Mite Allergen Der p 2 by Monocyte‐Derived Dendritic Cells and the Role of β2 Integrins

Monocyte‐derived dendritic cells (MDDC) are potent antigen‐presenting cells (APC). The APC functions of MDDC in allergy were examined. MDDC presentation of the major house dust mite allergen Der p 2 resulted in 4–12‐fold higher T‐cell proliferation and markedly higher IFN‐γ and IL‐5 production than PBMC cultures. Comparable T‐cell proliferation was obtained with 10‐fold fewer MDDC than purified monocytes. MDDC cultured from adherent cells, or CD14+, CD11b+ or Percoll‐purified monocytes were comparable in presenting soluble Ag, and in stimulating allogeneic MLR. Importantly, MDDC presentation of Der p 2 resulted in both Th1 and Th2 stimulation, although MDDC are known to produce high levels of IL‐12 and stimulate biased Th1 responses. The basis for the potent APC function of MDDC was further examined. MDDC were found to be highly phagocytic. Immunoprecipitation studies showed markedly elevated ICAM‐1 expression but > 10‐fold reduction in LFA‐1 expression on MDDC compared with monocytes. Monoclonal antibody (MoAb)‐blocking experiments showed that ICAM–LFA‐1 interaction was essential for MDDC stimulation of Der p 2‐specific T‐cell proliferative responses. These results show that the use of MDDC as APC provides a simple, sensitive and versatile method for detecting T‐cell responses to allergens and that the strong phagocytic capability and the increased ICAM‐1 expression of MDDC contribute significantly to their Ag presentation potency.
Skeletal muscle fiber, nerve, and blood vessel breakdown in space‐flown rats

Histochemical and ultrastructural analyses were performed postflight on hind limb skeletal muscles of rats orbited for 12.5 days aboard the unmanned Cosmos 1887 biosatellite and returned to Earth 2 days before sacrifice. The antigravity adductor longus (AL), soleus, and plantaris muscles atrophied more than the non‐weight‐bearing extensor digitorum longus, and slow muscle fibers were more atrophic than fast fibers. Muscle fiber segmental necrosis occurred selectively in the AL and soleus muscles; primarily, macrophages and neutrophils infiltrated and phagocytosed cellular debris. Granule‐rich mast cells were diminished in flight AL muscles compared with controls, indicating that mast cell secretion contributed to interstitial tissue edema. Increased ubiquitination of disrupted myofibrils implicated ubiquitin in myofilament degradation. Mitochondrial content and succinic dehydrogenase activity were normal, except for subsarcolemmal decreases. Myofibrillar ATPase activity of flight AL muscle fibers shifted toward the fast type. Absence of capillaries and extravasation of red blood cells indicated failed microcirculation. Muscle fiber regeneration from activated satellite cells was detected. About 17% of the flight AL end plates exhibited total or partial denervation. Thus, skeletal muscle weakness associated with spaceflight can result from muscle fiber atrophy and segmental necrosis, partial motor denervation, and disruption of the microcirculation. — Riley, D. A. ; Ilyina‐Kakueva, E. I. ; Ellis, S. ; Bain, J. L. W. ; Slocum, G. R. ; and Sedlak, F. R. Skeletal muscle fiber, nerve, and blood vessel breakdown in space‐flown rats. FASEB J 4: 84‐91; 1990.
Energetics of a strongly pH dependent RNA tertiary structure in a frameshifting pseudoknot.

Retroviruses employ -1 translational frameshifting to regulate the relative concentrations of structural and non-structural proteins critical to the viral life cycle. The 1.6 A crystal structure of the -1 frameshifting pseudoknot from beet western yellows virus reveals, in addition to Watson-Crick base-pairing, many loop-stem RNA tertiary structural interactions and a bound Na(+). Investigation of the thermodynamics of unfolding of the beet western yellows virus pseudoknot reveals strongly pH-dependent loop-stem tertiary structural interactions which stabilize the molecule, contributing a net of DeltaH approximately -30 kcal mol(-1) and DeltaG degrees (37) of -3.3 kcal mol(-1) to a total DeltaH and DeltaG degrees (37) of -121 and -16 kcal mol(-1), respectively, at pH 6.0, 0.5 M K(+) by DSC. Characterization of mutant RNAs supports the presence of a C8(+). G12-C26 loop 1-stem 2 base-triple (pK(a)=6.8), protonation of which contributes nearly -3.5 kcal mol(-1) in net stability in the presence of a wild-type loop 2. Substitution of the nucleotides in loop 2 with uridine bases, which would eliminate the minor groove triplex, destroys pseudoknot formation. An examination of the dependence of the monovalent ion and type on melting profiles suggests that tertiary structure unfolding occurs in a manner quantitatively consistent with previous studies on the stabilizing effects of K(+), NH(4)(+) and Na(+) on other simple duplex and pseudoknotted RNAs.
Development of the GABAergic System from Birth to Adolescence

The neurotransmitter GABA (γ-aminobutyric acid), acting via inotropic GABAA and metabotropic GABAB receptors, plays an essential role in a variety of distinct neuronal processes, including regulation of neuronal excitability, determination of temporal aspects of spike trains, control of the size and propagation of neuronal assemblies, generation of oscillatory activity, and neuronal plasticity. Although the developmental switch between excitatory and inhibitory GABAA receptor–mediated responses is widely appreciated, the fact that the postnatal maturation of the GABAergic system lasts until late adolescence is not so persuasively promoted. This review summarizes recent knowledge of the maturation of various aspects of the GABAergic systems, like functional expression of GABA synthesizing/degrading enzymes and transporters, density of GABAergic synapses, GABAergic projection patterns, GABA receptor subunit composition, and properties of GABAergic interneurons, with an emphasis on the late developmental alterations. In addition, some aspects of the development of mental capabilities during adolescence and their relation the delayed maturation of the GABAergic system are presented.
Nonlinear, interacting responses to climate limit grassland production under global change

Significance Global environmental change involves many factors that occur simultaneously, yet they are usually studied in isolation. Here we report a long-term global change experiment that subjected California grassland to multiple individual and simultaneous changes in temperature, precipitation, carbon dioxide, and nitrogen. Our analysis revealed nonlinear and interactive effects of temperature and precipitation on grassland net primary production (NPP), which defined a ridge-shaped NPP response surface to these two variables. Added nitrogen raised the peak of the NPP response surface, and added CO2 shifted the peak to lower temperatures. Our approach was validated by tests showing an absence of progressive effects over the years. In other ecosystems, our approach may be similarly powerful for probing the effects of multifactor global change. Global changes in climate, atmospheric composition, and pollutants are altering ecosystems and the goods and services they provide. Among approaches for predicting ecosystem responses, long-term observations and manipulative experiments can be powerful approaches for resolving single-factor and interactive effects of global changes on key metrics such as net primary production (NPP). Here we combine both approaches, developing multidimensional response surfaces for NPP based on the longest-running, best-replicated, most-multifactor global-change experiment at the ecosystem scale—a 17-y study of California grassland exposed to full-factorial warming, added precipitation, elevated CO2, and nitrogen deposition. Single-factor and interactive effects were not time-dependent, enabling us to analyze each year as a separate realization of the experiment and extract NPP as a continuous function of global-change factors. We found a ridge-shaped response surface in which NPP is humped (unimodal) in response to temperature and precipitation when CO2 and nitrogen are ambient, with peak NPP rising under elevated CO2 or nitrogen but also shifting to lower temperatures. Our results suggest that future climate change will push this ecosystem away from conditions that maximize NPP, but with large year-to-year variability.
Mechanism of Clostridium perfringens Enterotoxin Interaction with Claudin-3/-4 Protein Suggests Structural Modifications of the Toxin to Target Specific Claudins*

Background: Clostridium perfringens enterotoxin (CPE) binds to a subset of claudin tight junction proteins. Results: The molecular interface of the CPE-claudin interaction was mapped. Conclusion: Claudin-3 and -4 interact with CPE in the same orientation but in different modes. Significance: The mechanistic insights might advance design of CPE-based claudin modulators to improve paracellular drug delivery or to target claudin-overexpressing tumors. Claudins (Cld) are essential constituents of tight junctions. Domain I of Clostridium perfringens enterotoxin (cCPE) binds to the second extracellular loop (ECL2) of a subset of claudins, e.g. Cld3/4 and influences tight junction formation. We aimed to identify interacting interfaces and to alter claudin specificity of cCPE. Mutagenesis, binding assays, and molecular modeling were performed. Mutation-guided ECL2 docking of Cld3/4 onto the crystal structure of cCPE revealed a common orientation of the proposed ECL2 helix-turn-helix motif in the binding cavity of cCPE: residues Leu150/Leu151 of Cld3/4 bind similarly to a hydrophobic pit formed by Tyr306, Tyr310, and Tyr312 of cCPE, and Pro152/Ala153 of Cld3/4 is proposed to bind to a second pit close to Leu223, Leu254, and Leu315. However, sequence variation in ECL2 of these claudins is likely responsible for slightly different conformation in the turn region, which is in line with different cCPE interaction modes of Cld3 and Cld4. Substitutions of other so far not characterized cCPE residues lining the pocket revealed two spatially separated groups of residues (Leu223, Asp225, and Arg227 and Leu254, lle258, and Asp284), which are involved in binding to Cld3 and Cld4, albeit differently. Involvement of Asn148 of Cld3 in cCPE binding was confirmed, whereas no evidence for involvement of Lys156 or Arg157 was found. We show structure-based alteration of cCPE generating claudin binders, which interact subtype-specific preferentially either with Cld3 or with Cld4. The obtained mutants and mechanistic insights will advance the design of cCPE-based modulators to target specific claudin subtypes related either to paracellular barriers that impede drug delivery or to tumors.
Phenotypes of Chronic Obstructive Pulmonary Disease

The current clinical classification of smoking-related lung disease fails to take into account the heterogeneity of chronic obstructive pulmonary disease (COPD). With an increased understanding of pathophysiologic variation, COPD now clearly represents a spectrum of overlapping diseases with important extrapulmonary consequences. A “phenotype” describes the outward physical manifestations of a particular disease, and compromises anything that is part of the observable structure, function or behavior of an individual. Such phenotypic distinctions in COPD include: frequent exacerbator, pulmonary cachectic, rapid decliner, airways hyperresponsiveness, impaired exercise tolerance, and emphysema versus airways disease. These variable manifestations, each with unique prognostic, clinical and physiologic ramifications, represent distinct phenotypes within COPD. While all of these phenotypes have smoking as a common risk factor, the other risk factors that determine these phenotypes remain poorly understood. An individual smoker has variable expression of each phenotype and there is mounting evidence that COPD phenotypes have different clinical outcomes. These phenotypes can be broadly classified into one of three groups: clinical, physiologic and radiographic. This review presents the evidence for the spectrum of COPD phenotypes with a focused discussion on the pathophysiologic, epidemiologic and clinical significance of each subtype.
Initial evaluation of an Internet intervention to improve the sleep of cancer survivors with insomnia

Objective: Insomnia is a common complaint among cancer survivors. Fortunately, cognitive‐behavioral therapy for insomnia (CBT‐I) has been shown to be an effective treatment in this population. However, it is rarely implemented given its limited availability. To address this barrier, we examined the ability of an easily accessible online CBT‐I program to improve insomnia symptoms in cancer survivors.
Gender Differences in ADHD?

&NA; This study examined possible gender differences in children and adults with attention‐deficit/hyperactivity disorder. Results indicated that adult self‐ratings differed significantly by gender. Adult women reported fewer assets and more problems than did male counterparts, but there was no gender difference with respect to age at referral, intelligence quotient, indicators of neuropsychological performance, or parent or teacher ratings of behavior. Referral bias against girls is a possible reason for previously reported gender differences, so we interpreted our results in light of the participants' referral patterns. There was a nonsignificant trend for girls with relatively more severe ratings of hyperactivity, conduct disorder, or inattention to be referred earlier than were boys. Overall, our results suggest no evidence of cognitive or neuropsychological differences by gender in samples that are sensitive to behavioral deviance in girls (as evidenced by early referral), but adult women's self‐perception is comparatively poorer than that of adult men.
Développement précoce de la segmentation des formes sonores : unités rythmiques, voyelles puis consonnes

Les mots etant rarement produits hors contexte phrastique, les enfants vont devoir les extraire du flux de parole pour les apprendre. Les probabilites de transition (Saffran et al., 1996) et les unites rythmiques (Nazzi et al., 2006) seraient cruciales a l'emergence de la segmentation. Les formes sonores segmentees seront par la suite memorisees en representations phonetiquement detaillees. Cependant, selon Nespor et al. (2003) les consonnes seraient plus impliquees au niveau lexical que les voyelles, proposant un biais consonantique dans la reconnaissance des formes sonores segmentees. Le premier axe de ma these s'interesse aux capacites precoces de segmentation chez les enfants francophones nes a terme et prematures afin de determiner quand elles emergent et dans quelle mesure les unites rythmiques sont impliquees. Le second s'interesse a l'emergence et a l'origine du biais consonantique. Les resultats montrent que (1) les enfants nes a terme et prematures sont capables de segmenter la parole en utilisant l'unite syllabique des 6 mois ; (2) d'un biais vocalique a 6 mois, les enfants francophones, acquierent un biais consonantique a 8 mois dans la reconnaissance de formes sonores segmentees ; (3) le biais consonantique proviendrait donc de l'acquisition des proprietes acoustiques/phonetiques de la langue maternelle.
Muscle fibre conduction velocity in motor units of the human anterior tibial muscle: a new size principle parameter.

1. Twitch contractions were elicited in human anterior tibial muscle by intramuscular microstimulation of single motor axons with a bipolar needle electrode. The population of stimulated motor units studied was fairly representative for the muscle. 2. The conduction velocity of the fibres in the motor unit was calculated as the ratio between the electrode separation (15 mm) in a tripolar array of surface electrodes and the conduction delay of the motor unit potential along the electrode array. The motor unit conduction velocity ranged from 2.6 to 5.3 m/s with a mean of 3.7 m/s. 3. The contractile properties of the motor units were obtained by averaging the torque developed around the ankle joint. Twitch torques ranged from less than 10(‐3) to 16 x 10(‐3) N m, with a mean of 5.7 x 10(‐3) N m. The twitch torque of the whole anterior tibial muscle was approximately 5 N m. Rise times were 47‐80 m/s with a mean of 61 m/s, and half‐relaxation times were 40‐78 ms with a mean of 60 ms. 4. The mechanical properties of individual motor units were highly correlated (rise time and twitch torque: r = ‐0.81; rise time and half‐relaxation time: r = 0.75; twitch torque and half‐relaxation time: r = ‐0.81). 5. The motor unit conduction velocity was highly correlated to twitch torque (r = 0.87), rise time (r = ‐0.75) and half‐relaxation time (r = ‐0.66). This indicates that the motor unit conduction velocity can be included in the family of interrelated 'size principle parameters'.
Perception of Pain and Exertion During Exercise on a Cycle Ergometer in Chronic Pain Patients

Hypothesis:Chronic pain patients (CPP) are generally thought to present with reduced fitness in relation with pain enhancement during exercise. A distortion of exertion perception may coexist, which could lead CPP to reduce physical activities. Design:Case-control study, with a nonrandomized consecutive sample that was age matched. Setting:A Chronic Pain Unit in a Multidisciplinary Pain Center of a university hospital in a city of > 1,000,000 inhabitants. Subjects:42 CPP referred for evaluation and 34 controls (staff members and relatives). Outcome measures:Fitness index and exertion perception index was obtained by a cycle ergometer test. Trend analysis was performed on pain scores reported on a visual analogue scale during exertion. Results:Male CPP mean fitness index was found to be significantly reduced. No difference in exertion perception was found between groups. Trend analysis of reported pain revealed that 49% of CPP showed a positive trend, 5% a negative trend, and 46% showed no significant trend as exercise intensity increased. There was no significant relation between type of trend and fitness nor exertion perception index. Conclusions:Only male CPP have a reduced work capacity. Exertion perception seems normal among CPP. The possible distortion of exertion perception as a causal factor in the reduced fitness of CPP has to be rejected. Lack of significant correlation between type of trend of pain while exercising on a cycle ergometer and fitness index shows that one should be careful in proposing that reduced fitness is only related to pain enhancement during exercise in CPP.
Serum levels of vitamin D, PTH and calcium and breast cancer risk—a prospective nested case–control study

Previous studies indicate that calcium and its regulating hormones, i.e., parathyroid hormone (PTH) and vitamin D, might affect breast cancer risk. Evidence also suggests that this relationship could be influenced by menopausal status and BMI. We examined breast cancer risk related to prediagnostic serum levels of vitamin D (25OHD2 and 25OHD3), PTH and calcium using a nested case–control design within the Malmö Diet and Cancer Study. There were 764 incident breast cancer cases, and 764 controls were selected by incidence density matching, using age as the underlying time scale, matching on calendar time at inclusion, menopausal status and age at inclusion. Using logistic regression analysis, odds ratios (OR) with 95% confidence intervals were calculated for breast cancer risk in different quartiles of the analyzed factors. All analyses were adjusted for risk factors for breast cancer, and for levels of albumin, creatinine and phosphate. Analyses were repeated stratified for BMI and menopausal status, and for low vs. high levels of 25OHD3, PTH and calcium. There was a weak, nonsignificant inverse association between breast cancer risk and 25OHD3, and the OR for the 2nd, 3rd and 4th quartiles, as compared to the first, were 0.84 (0.60–1.15), 0.84 (0.60–1.17) and 0.93 (0.66–1.33). Serum calcium was positively associated with breast cancer in premenopausal women (OR for the 4th quartile = 3.10:1.33–7.22 and p for quartile trend = 0.04), and in women with BMI > 25 (OR for the 4th quartile = 1.94:1.12–3.37 and p for trend < 0.01). There was no association between baseline serum PTH and breast cancer risk.
Growth of Hmong children.

OBJECTIVE To investigate the growth of a group of young Hmong children. DESIGN In this descriptive, comparative study, length and weight measures of Hmong children were abstracted from medical charts for each previous clinic visit (newborn to most recent visit) where both measures had been recorded, and measures were compared with National Center for Health Statistics (NCHS) standard percentiles. Visits occurred from 1988 to 1994. PARTICIPANTS AND SETTING Participants were 579 Hmong children, ages 0 to 5 years, who were active patients at a family practice residency clinic. MAIN OUTCOME MEASURES Length and weight. RESULTS This group of Hmong children showed lengths similar to those of the NCHS reference population for the first 6 to 12 months of life, after which they lagged behind reference lengths. By the 24th month, median length for Hmong girls and boys was less than the NCHS 25th percentile. The Hmong children's average weight was slightly higher than the NCHS median until about 8 months of age, after which the distributions were similar. CONCLUSIONS Compared with children who comprise the NCHS reference population, the Hmong children in this study were slightly heavier in the first several months of life, and shorter thereafter. Therefore, in general, the Hmong children were proportionately heavier than other children of similar height.