Genome-wide profiling of the cardiac transcriptome after myocardial infarction identifies novel heart-specific long non-coding RNAs.

AIM: Heart disease is recognized as a consequence of dysregulation of cardiac gene regulatory networks. Previously, unappreciated components of such networks are the long non-coding RNAs (lncRNAs). Their roles in the heart remain to be elucidated. Thus, this study aimed to systematically characterize the cardiac long non-coding transcriptome post-myocardial infarction and to elucidate their potential roles in cardiac homoeostasis. METHODS AND RESULTS: We annotated the mouse transcriptome after myocardial infarction via RNA sequencing and ab initio transcript reconstruction, and integrated genome-wide approaches to associate specific lncRNAs with developmental processes and physiological parameters. Expression of specific lncRNAs strongly correlated with defined parameters of cardiac dimensions and function. Using chromatin maps to infer lncRNA function, we identified many with potential roles in cardiogenesis and pathological remodelling. The vast majority was associated with active cardiac-specific enhancers. Importantly, oligonucleotide-mediated knockdown implicated novel lncRNAs in controlling expression of key regulatory proteins involved in cardiogenesis. Finally, we identified hundreds of human orthologues and demonstrate that particular candidates were differentially modulated in human heart disease. CONCLUSION: These findings reveal hundreds of novel heart-specific lncRNAs with unique regulatory and functional characteristics relevant to maladaptive remodelling, cardiac function and possibly cardiac regeneration. This new class of molecules represents potential therapeutic targets for cardiac disease. Furthermore, their exquisite correlation with cardiac physiology renders them attractive candidate biomarkers to be used in the clinic.

Modelling of iron-filled magneto-active polymers with a dispersed chain-like microstructure

Magneto-active polymers are a class of smart materials commonly manufactured by mixing micron-sized iron particles in a rubber-like matrix. When cured in the presence of an externally applied magnetic field, the iron particles arrange themselves into chain-like structures that lend an overall anisotropy to the material. It has been observed through electron micrographs and X-ray tomographs that these chains are not always perfect in structure, and may have dispersion due to the conditions present during manufacturing or some undesirable material properties. We model the response of these materials to coupled magneto-mechanical loading in this paper using a probability based structure tensor that accounts for this imperfect anisotropy. The response of the matrix material is decoupled from the chain phase, though still being connected through kinematic constraints. The latter is based on the definition of a 'chain deformation gradient' and a 'chain magnetic field'. We conclude with numerical examples that demonstrate the effect of chain dispersion on the response of the material to magnetoelastic loading.

Functional importance of cardiac enhancer-associated noncoding RNAs in heart development and disease.

The key information processing units within gene regulatory networks are enhancers. Enhancer activity is associated with the production of tissue-specific noncoding RNAs, yet the existence of such transcripts during cardiac development has not been established. Using an integrated genomic approach, we demonstrate that fetal cardiac enhancers generate long noncoding RNAs (lncRNAs) during cardiac differentiation and morphogenesis. Enhancer expression correlates with the emergence of active enhancer chromatin states, the initiation of RNA polymerase II at enhancer loci and expression of target genes. Orthologous human sequences are also transcribed in fetal human hearts and cardiac progenitor cells. Through a systematic bioinformatic analysis, we identified and characterized, for the first time, a catalog of lncRNAs that are expressed during embryonic stem cell differentiation into cardiomyocytes and associated with active cardiac enhancer sequences. RNA-sequencing demonstrates that many of these transcripts are polyadenylated, multi-exonic long noncoding RNAs. Moreover, knockdown of two enhancer-associated lncRNAs resulted in the specific downregulation of their predicted target genes. Interestingly, the reactivation of the fetal gene program, a hallmark of the stress response in the adult heart, is accompanied by increased expression of fetal cardiac enhancer transcripts. Altogether, these findings demonstrate that the activity of cardiac enhancers and expression of their target genes are associated with the production of enhancer-derived lncRNAs.

Comparison of Four Sections for Analyzing Running Mechanics Alterations During Repeated Treadmill Sprints.

We compared different approaches to analyze running mechanics alterations during repeated treadmill sprints. Thirteen active male athletes performed five 5-second sprints with 25 seconds of recovery on an instrumented treadmill. This approach allowed continuous measurement of running kinetics/kinematics and calculation of vertical and leg stiffness variables that were subsequently averaged over 3 distinct sections of the 5-second sprint (steps 2-5, 7-10, and 12-15) and for all steps (steps 2-15). Independently from the analyzed section, propulsive power and step frequency decreased with fatigue, while contact time and step length increased (P < .05). Except for step frequency, all mechanical variables varied (P < .05) across sprint sections. The only parameters that highly depend on running velocity (propulsive power and vertical stiffness) showed a significant interaction (P < .05) between the analyzed sections, with smaller magnitude of fatigue-induced change observed for steps 2-5. Considering all steps or only a few steps during early, middle, or late phases of 5-second sprints provides similar mechanical outcomes during repeated treadmill sprinting, although acceleration induces noticeable differences between the sections studied. Furthermore, quantifying mechanical alterations from the early acceleration phase may not be readily detectable, and is not recommended.

An active zone characterized by slow normal faults, the northwestern margin of the València trough (NE Iberia): a review

The northwestern margin of the Valencia trough is an area of low strain characterized by slow normal faults and low to moderate seismicity. Since the mid 1990s this area has been the subject of a number of studies on active tectonic which have proposed different approaches to the location of active faults and to the calculation of the parameters that describe their seismic cycle. Fifty-six active faults have been found and a classification has been made in accordance with their characteristics: a) faults with clear evidence of large paleo-, historic or instrumental earthquakes (2/56); b) faults with evidence of accumulated activity during the Plio-Quaternary and with associated instrumental seismicity (7/56); c) faults with evidence of accumulated activity during the Plio-Quaternary and without associated instrumental seismicity (17/56); d) faults with associated instrumental seismicity and without evidence of accumulated activity during the Plio-Quaternary (30/56), and e) faults without evidence of activity or inactive faults. The parameters that describe the seismic cycle of these faults have been evaluated by different methods that use the geological data obtained for each fault except when paleoseismological studies were available. This classification can be applied to other areas with low slip faults because of the simplicity of the approaches adopted. This study reviews the different approaches proposed and describes the active faults located, highlighting the need a) to better understand active faults in slow strain zones through paleoseismological studies, and b) to include them in seismic hazard studies.

Genomic and transcriptomic analysis of the streptomycin-dependent Mycobacterium tuberculosis strain 18b.

The ability of Mycobacterium tuberculosis to establish a latent infection (LTBI) in humans confounds the treatment of tuberculosis. Consequently, there is a need to discover new therapeutic agents that can kill M. tuberculosis both during active disease and LTBI. The streptomycin-dependent strain of M. tuberculosis, 18b, provides a useful tool for this purpose since upon removal of streptomycin (STR) it enters a non-replicating state that mimics latency both in vitro and in animal models. The 4.41 Mb genome sequence of M. tuberculosis 18b was determined and this revealed the strain to belong to clade 3 of the ancient ancestral lineage of the Beijing family. STR-dependence was attributable to insertion of a single cytosine in the 530 loop of the 16S rRNA and to a single amino acid insertion in the N-terminal domain of initiation factor 3. RNA-seq was used to understand the genetic programme activated upon STR-withdrawal and hence to gain insight into LTBI. This revealed reconfiguration of gene expression and metabolic pathways showing strong similarities between non-replicating 18b and M. tuberculosis residing within macrophages, and with the core stationary phase and microaerophilic responses. The findings of this investigation confirm the validity of 18b as a model for LTBI, and provide insight into both the evolution of tubercle bacilli and the functioning of the ribosome.

Strain and strain rate by two-dimensional speckle tracking echocardiography in a maned wolf

The measurement of cardiovascular features of wild animals is important, as is the measurement in pets, for the assessment of myocardial function and the early detection of cardiac abnormalities, which could progress to heart failure. Speckle tracking echocardiography (2D STE) is a new tool that has been used in veterinary medicine, which demonstrates several advantages, such as angle independence and the possibility to provide the early diagnosis of myocardial alterations. The aim of this study was to evaluate the left myocardial function in a maned wolf by 2D STE. Thus, the longitudinal, circumferential and radial strain and strain rate were obtained, as well as, the radial and longitudinal velocity and displacement values, from the right parasternal long axis four-chamber view, the left parasternal apical four chamber view and the parasternal short axis at the level of the papillary muscles. The results of the longitudinal variables were -13.52±7.88, -1.60±1.05, 4.34±2.52 and 3.86±3.04 for strain (%), strain rate (1/s), displacement (mm) and velocity (cm/s), respectively. In addition, the radial and circumferential Strain and Strain rate were 24.39±14.23, 1.86±0.95 and -13.69±6.53, -1.01±0.48, respectively. Thus, the present study provides the first data regarding the use of this tool in maned wolves, allowing a more complete quantification of myocardial function in this species.

Ovariectomy does not affect the cardiac sympathovagal balance of female SHR but estradiol does

The low incidence of cardiovascular diseases, including hypertension, in premenopausal women has led to the conclusion that ovarian hormones may have a protective effect on the cardiovascular system. We evaluated the effects of ovariectomy and/or estradiol on sympathovagal balance and heart rate variability (HRV) in female spontaneously hypertensive rats (SHR) with tachycardia and compared them to Wistar rats (12 weeks old; N = 8-12). Ovariectomy (OVX) and/or estradiol (10 µg/kg) did not affect basal arterial pressure in either rat strain, but estradiol increased basal heart rate (HR) in OVX SHR (454 ± 18 vs 377 ± 9 bpm). HR changes elicited by methylatropine and propranolol were used to evaluate the sympathovagal balance. Ovariectomy did not affect the cardiac sympathovagal balance of any group, while estradiol increased sympathetic tone in OVX SHR (120 ± 8 vs 56 ± 10 bpm) and sham-operated Wistar rats (57 ± 7 vs 28 ± 4 bpm), and decreased the parasympathetic tone only in OVX SHR (26 ± 7 vs 37 ± 5 bpm). HRV was studied in the frequency domain (Fast Fourier Transformation). Spectra of HR series were examined at low frequency (LF: 0.2-0.75 Hz) and high frequency (HF: 0.75-3 Hz) bands. The power of LF, as well as the LF/HF ratio, was not affected by ovariectomy, but estradiol increased both LF (29 ± 4 vs 18 ± 3 nu in Wistar sham-operated, 26 ± 5 vs 15 ± 3 nu in Wistar OVX, 50 ± 3 vs 38 ± 4 nu in SHR sham-operated, and 51 ± 3 vs 42 ± 3 nu in SHR OVX) and LF/HF (0.48 ± 0.08 vs 0.23 ± 0.03 nu in Wistar sham-operated, 0.41 ± 0.14 vs 0.19 ± 0.05 nu in Wistar OVX, 0.98 ± 0.11 vs 0.63 ± 0.11 nu in SHR sham-operated, and 1.10 ± 0.11 vs 0.78 ± 0.1 nu in SHR OVX). Thus, we suggest that ovariectomy did not affect the cardiac sympathovagal balance of SHR or Wistar rats, while estradiol increased the sympathetic modulation of HR.

Psychiatric disorders and cardiac anxiety in exercising and sedentary coronary artery disease patients: a case-control study

Regular physical exercise has been shown to favorably influence mood and anxiety; however, there are few studies regarding psychiatric aspects of physically active patients with coronary artery disease (CAD). The objective of the present study was to compare the prevalence of psychiatric disorders and cardiac anxiety in sedentary and exercising CAD patients. A total sample of 119 CAD patients (74 men) were enrolled in a case-control study. The subjects were interviewed to identify psychiatric disorders and responded to the Cardiac Anxiety Questionnaire. In the exercise group (N = 60), there was a lower prevalence (45 vs 81%; P < 0.001) of at least one psychiatric diagnosis, as well as multiple comorbidities, when compared to the sedentary group (N = 59). Considering the Cardiac Anxiety Questionnaire, sedentary patients presented higher scores compared to exercisers (mean ± SEM = 55.8 ± 1.9 vs 37.3 ± 1.6; P < 0.001). In a regression model, to be attending a medically supervised exercise program presented a relevant potential for a 35% reduction in cardiac anxiety. CAD patients regularly attending an exercise program presented less current psychiatric diagnoses and multiple mental-related comorbidities and lower scores of cardiac anxiety. These salutary mental effects add to the already known health benefits of exercise for CAD patients.

Pro-fibrotic role of ERK3-MK5 during pressure-overload induced cardiac hypertrophy

Il y a 4 isoforme de p38 : α, β, δ, and γ. MK5, à l'origine identifié comme étant un régulateur de PRAK (Regulated/Activated Protein Kinase), est maintenant connu pour être activée par la protéine kinase p38 (qui est un mitogène activé par la protéine kinase, MAPK). Cette dernière est impliquée dans les mécanismes de fibrose et d'apoptose pendant l'hypertrophie cardiaque. De plus, MK5 est également activée par les MAPKs atypiques; ERK3 et ERK4. Bien qu’elles soient fortement exprimées dans le coeur, le rôle physiologique de MK5 et ERK3 demeure inconnu. Par conséquent, nous avons étudié l'effet de la constriction aortique transversale (TAC) – induisant un surcharge chronique de pression chez les souris hétèrozygotes knockout pour MK5 (MK5+/-) ou ERK3 (ERK3+/-) et pour leurs types sauvages (MK5+/+ et ERK3+/+). Deux sem post-TAC; le ratio de poids du coeur/poids corporel a été augmenté chez les 2 souris MK5+/- et MK5+/+. L'échocardiographie de la trans-thoracique démontre que la surcharge de pression a altéré la fonction diastolique du ventricule gauche chez MK5+/+, mais pas chez la souris MK5+/-. De plus, nous avons observé moins de dépôt de collagène, évalué par une coloration au trichrome de Masson, 2 et 3 sem post-TAC chez les souris MK5+/-. Parallèlement, le niveau de l’ARNm de collagène type1 alpha-1 a été significativement diminué dans les coeurs des souris MK5+/-, 2 et 3 sem post-TAC. De même, ERK3, mais pas ERK5 ni p38α, co-IP avec MK5 dans les 2 modèles des coeurs TAC; aigus ou chroniques. En revanche, l’ajout exogénique de GST-MK5 a abaissé ERK4 et p38α, mais pas ERK3 dans les lysâtes de coeur de souris. Par contre, GST-ERK3 et GST-p38α ne démontrent aucune co-IP avec MK5. Ces données suggèrent que dans le coeur seul ERK3, et non ERK4 ou p38α, est capable d’interagir avec, et réguler MK5. A niveau physiologique MK5 interagit entièrement avec ERK3 et par conséquent MK5 n’est pas disponible pour lier les protéines exogéniques. Les souris hétérozygotes pour ERK3 (ERK3+/-) ont également démontré une réduction ou une absence de collagène et une faible expression d’ARNm du collagène type1 alpha1, 3 sem post-TAC. Ces résultats démontrent un important rôle pro-fibrotique de la signalisation MK5-ERK3 pendant une surcharge chronique de pression.Nous avons également démontré 5 variant d'épissage de (MK5.1-5), y compris la forme originale (MK5.1). MK5.2 et MK5.5 subissent une délétion de 6 paires de base dans l’exon 12 : MK5.3 manque l'exon 12 : MK5.4 et MK5.5 manquent les exons 2-6. L'expression des ARNm des différents variant d'épissage a été vérifiée par PCR en temps réel (qPCR). Bien que l’expression est ubiquitaire, l'abondance relative de chaque variant était tissu-spécifique (coeur, rein, pancréas, muscle squelettique, poumon, foie, et cerveau). En plus, l'abondance relative des variant d’épissage varie pendant la surcharge de pression et le développement postnatal du coeur. En outre, l'immunofluorescence a indiqué que MK5.1-5.3 se localise au noyau alors que MK5.4-5.5 est situé au niveau cytoplasmic dans les cellules HEK 293 non stimulées. Suite à une stimulation avec l'anisomycin, un activateur de p38 MAPK, MK5.1-5.3 se translocalise du noyau au cytoplasme alors qu’une petite fraction de MK5.4-5.5 translocalise vers le noyau. Ces variant d'épissage peuvent diversifier la signalisation de MK5-ERK3 dans coeur, mais leur rôle exact oblige des recherches supplémentaires. Excepté l’isoforme δ, toutes les isoformes de p38 sont exprimées dans le coeur et la forme α est considérée comme étant l'isoforme dominante. L’analyse par qPCR et immunobuvardage de type western ont démontré que p38α et p38γ sont les deux isoformes prédominantes alors que p38β et p38δ sont exprimées aux mêmes niveaux dans le coeur de rat adulte. L'immunofluorescence a démontré que p38α et p38γ se trouvent dans le cytoplasme et le noyau. Cependant, suite à la surcharge par TAC, p38γ s'est accumulé dans noyau tandis que la distribution de p38α est demeurée inchangée. Ainsi, l'abondance de p38γ et sa translocalisation nucléaire suite à la surcharge de pression indique un rôle potentiel dans l'expression génique pendant le remodelage cardiaque. En conclusion, nous avons mis en évidence pour la première fois un rôle pro-fibrotique pour la signalisation MK5-ERK3 pendant une surcharge chronique de pression. D'ailleurs, les niveaux comparables d'expression de p38γ avec p38α, et la localisation différentielle de p38γ pendant la surcharge aiguë ou chronique de pression suggèrent différents rôles possibles pour ces isoformes pendant le remodelage hypertrophique cardiaque.

Analysis of intrinsic cardiac neuron activity in relation to neurogenic atrial fibrillation and vagal stimulation

La fibrillation auriculaire est le trouble du rythme le plus fréquent chez l'homme. Elle conduit souvent à de graves complications telles que l'insuffisance cardiaque et les accidents vasculaires cérébraux. Un mécanisme neurogène de la fibrillation auriculaire mis en évidence. L'induction de tachyarythmie par stimulation du nerf médiastinal a été proposée comme modèle pour étudier la fibrillation auriculaire neurogène. Dans cette thèse, nous avons étudié l'activité des neurones cardiaques intrinsèques et leurs interactions à l'intérieur des plexus ganglionnaires de l'oreillette droite dans un modèle canin de la fibrillation auriculaire neurogène. Ces activités ont été enregistrées par un réseau multicanal de microélectrodes empalé dans le plexus ganglionnaire de l'oreillette droite. L'enregistrement de l'activité neuronale a été effectué continument sur une période de près de 4 heures comprenant différentes interventions vasculaires (occlusion de l'aorte, de la veine cave inférieure, puis de l'artère coronaire descendante antérieure gauche), des stimuli mécaniques (toucher de l'oreillette ou du ventricule) et électriques (stimulation du nerf vague ou des ganglions stellaires) ainsi que des épisodes induits de fibrillation auriculaire. L'identification et la classification neuronale ont été effectuées en utilisant l'analyse en composantes principales et le partitionnement de données (cluster analysis) dans le logiciel Spike2. Une nouvelle méthode basée sur l'analyse en composante principale est proposée pour annuler l'activité auriculaire superposée sur le signal neuronal et ainsi augmenter la précision de l'identification de la réponse neuronale et de la classification. En se basant sur la réponse neuronale, nous avons défini des sous-types de neurones (afférent, efférent et les neurones des circuits locaux). Leur activité liée à différents facteurs de stress nous ont permis de fournir une description plus détaillée du système nerveux cardiaque intrinsèque. La majorité des neurones enregistrés ont réagi à des épisodes de fibrillation auriculaire en devenant plus actifs. Cette hyperactivité des neurones cardiaques intrinsèques suggère que le contrôle de cette activité pourrait aider à prévenir la fibrillation auriculaire neurogène. Puisque la stimulation à basse intensité du nerf vague affaiblit l'activité neuronale cardiaque intrinsèque (en particulier pour les neurones afférents et convergents des circuits locaux), nous avons examiné si cette intervention pouvait être appliquée comme thérapie pour la fibrillation auriculaire. Nos résultats montrent que la stimulation du nerf vague droit a été en mesure d'atténuer la fibrillation auriculaire dans 12 des 16 cas malgré un effet pro-arythmique défavorable dans 1 des 16 cas. L'action protective a diminué au fil du temps et est devenue inefficace après ~ 40 minutes après 3 minutes de stimulation du nerf vague.

Strain longitudinal global para la detección de estenosis coronaria significativa en pacientes con infarto agudo del miocardio

Introducción: La evaluación de la función miocárdica global y regional juega una papel crítico en el diagnóstico y manejo de los pacientes con enfermedad coronaria con importantes implicaciones pronosticas, las nuevas técnicas ecocardiográficas como la evaluación del STRAIN han sido validadas como una herramienta objetiva, comprehensiva y precisa para evaluar dichos parámetros. Objetivo: Determinar la capacidad del strain global longitudinal para la detección de estenosis coronaria significativa, número de territorios comprometidos y territorio anatómico del vaso culpable; en pacientes sin antecedentes de enfermedad coronaria previa con infarto agudo del miocardio. Diseño: estudio de pruebas diagnósticas retrospectivo en el que se utilizó como gold estándar la angiografía coronaria, se seleccionaron 64 pacientes con ecocardiograma transtorácico previo a la angiografía coronaria. Resultados: Se demostró una exactitud intermedia del strain global longitudinal para detectar estenosis coronaria por análisis de curvas ROC, con un área bajo la curva de 0,78 p= 0,000 (IC 0,6; 1,0), Una sensibilidad de 96.5% (91.7%, 101.3%), especificidad 40.0% (9.6%, 70.4%) y una prevalencia real del enfermedad coronaria de 85.1% (76.5%, 93.6%) Conclusiones: La medición de la función global y regional por medio del strain global longitudinal identifica pacientes con infarto agudo del miocardio que tienen estenosis coronaria significativa, número de territorios afectados, y la distribución anatómica de los posibles vasos culpables, sin embargo hay que tener precaución en su uso que sólo se limite a escenarios en donde pueda ser interpretado adecuadamente. Palabras clave: strain global bidimensional, detección de estenosis coronaria significativa, infarto del miocardio.

Mecánica ventricular izquierda en pacientes con infarto agudo del miocardio

RESUMEN Introducción El papel de las nuevas técnicas ecocardiográficas para el diagnóstico de infarto agudo del miocardio se encuentra en desarrollo y la realización de mecánica ventricular izquierda podría sugerir la presencia de enfermedad coronaria hemodinámicamente significativa. Objetivos Determinar si en pacientes con infarto agudo del miocardio la medición de strain longitudinal global y regional sirve para predecir la presencia de enfermedad coronaria significativa. Métodos Es un estudio de pruebas diagnósticas en el que se evaluaron las características operativas de la mecánica ventricular izquierda para la detección de enfermedad coronaria significativa comparado contra el cateterismo cardiaco, considerado el patrón de oro. Se analizaron 54 pacientes con infarto agudo del miocardio llevados a cateterismo cardiaco, a quienes se les realizó un ecocardiograma transtorácico con medición de strain longitudinal global y regional. Resultados De los 54 pacientes analizados, el 83% tenía enfermedad coronaria significativa. El hallazgo de un strain longitudinal global < -17.5 tuvo una sensibilidad del 85% y una especificidad del 78% para predecir la presencia de enfermedad coronaria; para la arteria descendente anterior un strain longitudinal regional < – 17.4 tuvo una sensibilidad de 82% y una especificidad de 44%, para la arteria circunfleja una sensibilidad del 87% y una especificidad del 37% y para la arteria coronaria derecha una sensibilidad de 73% y una especificidad de 32%. Conclusiones La realización de ecocardiografía con mecánica ventricular en pacientes con infarto agudo del miocardio es útil para predecir la presencia de enfermedad coronaria hemodinámicamente significativa.

Deforming glassy polystyrene: Influence of pressure, thermal history, and deformation mode on yielding and hardening

The toughness of a polymer glass is determined by the interplay of yielding, strain softening, and strain hardening. Molecular-dynamics simulations of a typical polymer glass, atactic polystyrene, under the influence of active deformation have been carried out to enlighten these processes. It is observed that the dominant interaction for the yield peak is of interchain nature and for the strain hardening of intrachain nature. A connection is made with the microscopic cage-to-cage motion. It is found that the deformation does not lead to complete erasure of the thermal history but that differences persist at large length scales. Also we find that the strain-hardening modulus increases with increasing external pressure. This new observation cannot be explained by current theories such as the one based on the entanglement picture and the inclusion of this effect will lead to an improvement in constitutive modeling.

Microscopic Mechanisms of Strain Hardening in Glassy Polymers

The mechanisms underlying the increase in stress for large mechanical strains of a polymer glass, quantified by the strain-hardening modulus, are still poorly understood. In the present paper we aim to elucidate this matter and present new mechanisms. Molecular-dynamics simulations of two polymers with very different strain-hardening moduli (polycarbonate and polystyrene) have been carried out. Nonaffine displacements occur because of steric hindrances and connectivity constraints. We argue that it is not necessary to introduce the concept of entanglements to understand strain hardening, but that hardening is rather coupled with the increase in the rate of nonaffine particle displacements. This rate increases faster for polycarbonate, which has the higher strain-hardening modulus. Also more nonaffine chain stretching is present for polycarbonate. It is shown that the inner distances of such a nonaffinely deformed chain can be well described by the inner distances of the worm-like chain, but with an effective stiffness length (equal to the Kuhn length for an infinite worm-like chain) that increases during deformation. It originates from the finite extensibility of the chain. In this way the increase in nonaffine particle displacement can be understood as resulting from an increase in the effective stiffness length of the perturbed chain during deformation, so that at larger strains a higher rate of plastic events in terms of nonaffine displacement is necessary, causing in turn the observed strain hardening in polymer glasses.