Array Of Domains Research Articles

The mycobacterial PhoH2 proteins are type II toxin antitoxins coupled to RNA helicase domains

PhoH2 proteins are found in a diverse range of organisms that span the bacterial tree and little is known about this large protein family. PhoH2 proteins have two domains: An N-terminal PIN domain fused to a C-terminal PhoH domain. The genome of Mycobacterium tuberculosis encodes 48 PIN domains and 47 of these constitute the VapC components of the 47 VapBC toxin-antitoxins. The 48th member of the M. tuberculosis PIN domain array is found in the single PhoH2 protein encoded in the genome. All characterized PIN domain proteins are RNases and the PhoH domains are predicted ATPases. This fusion of a PIN domain with an ATPase reflects a much wider association between PIN domains and PhoH domains across many prokaryote genomes. Here, we examine PhoH2 proteins from M. tuberculosis, Mycobacterium smegmatis and a thermophilic homologue from Thermobispora bispora and we show that PhoH2 is a sequence-specific RNA helicase and RNAse. In addition, phoH2 from M. tuberculosis and M. smegmatis is part of a longer mRNA transcript which includes a small, unannotated open reading frame (ORF) upstream of the phoH2 gene. This small gene overlaps with the beginning of the phoH2 gene in a manner similar to the PIN domain toxin-antitoxin operons. We have annotated the upstream gene as phoAT and its putative promoter elements satisfy previously characterized consensus sequences at the-10 site. Conditional growth experiments carried out in M. smegmatis revealed a negative effect on growth by the expression of M. tuberculosis PhoH2 that was alleviated by co-expression of the PhoAT peptide. Thus in M. tuberculosis, PhoH2 represents a new variation on a type II PIN domain toxin-antitoxin systems such that the toxin-antitoxin is now coupled to an RNA helicase whose predicted biological function is to unwind and cleave RNA in a sequence specific manner.

Drosophila melanogaster Mini Spindles TOG3 Utilizes Unique Structural Elements to Promote Domain Stability and Maintain a TOG1- and TOG2-like Tubulin-binding Surface

Microtubule-associated proteins regulate microtubule (MT) dynamics spatially and temporally, which is essential for proper formation of the bipolar mitotic spindle. The XMAP215 family is comprised of conserved microtubule-associated proteins that use an array of tubulin-binding tumor overexpressed gene (TOG) domains, consisting of six (A-F) Huntingtin, elongation factor 3, protein phosphatase 2A, target of rapamycin (HEAT) repeats, to robustly increase MT plus-end polymerization rates. Recent work showed that TOG domains have differentially conserved architectures across the array, with implications for position-dependent TOG domain tubulin binding activities and function within the XMAP215 MT polymerization mechanism. Although TOG domains 1, 2, and 4 are well described, structural and mechanistic information characterizing TOG domains 3 and 5 is outstanding. Here, we present the structure and characterization of Drosophila melanogaster Mini spindles (Msps) TOG3. Msps TOG3 has two unique features as follows: the first is a C-terminal tail that stabilizes the ultimate four HEAT repeats (HRs), and the second is a unique architecture in HR B. Structural alignments of TOG3 with other TOG domain structures show that the architecture of TOG3 is most similar to TOG domains 1 and 2 and diverges from TOG4. Docking TOG3 onto recently solved Stu2 TOG1· and TOG2·tubulin complex structures suggests that TOG3 uses similarly conserved tubulin-binding intra-HEAT loop residues to engage α- and β-tubulin. This indicates that TOG3 has maintained a TOG1- and TOG2-like TOG-tubulin binding mode despite structural divergence. The similarity of TOG domains 1-3 and the divergence of TOG4 suggest that a TOG domain array with polarized structural diversity may play a key mechanistic role in XMAP215-dependent MT polymerization activity.

Single-step deposition of high-mobility graphene at reduced temperatures.

Current methods of chemical vapour deposition (CVD) of graphene on copper are complicated by multiple processing steps and by high temperatures required in both preparing the copper and inducing subsequent film growth. Here we demonstrate a plasma-enhanced CVD chemistry that enables the entire process to take place in a single step, at reduced temperatures (<420 °C), and in a matter of minutes. Growth on copper foils is found to nucleate from arrays of well-aligned domains, and the ensuing films possess sub-nanometre smoothness, excellent crystalline quality, low strain, few defects and room-temperature electrical mobility up to (6.0±1.0) × 10(4) cm(2) V(-1) s(-1), better than that of large, single-crystalline graphene derived from thermal CVD growth. These results indicate that elevated temperatures and crystalline substrates are not necessary for synthesizing high-quality graphene.

Magnetic bubblecade memory based on chiral domain walls.

Unidirectional motion of magnetic domain walls is the key concept underlying next-generation domain-wall-mediated memory and logic devices. Such motion has been achieved either by injecting large electric currents into nanowires or by employing domain-wall tension induced by sophisticated structural modulation. Herein, we demonstrate a new scheme without any current injection or structural modulation. This scheme utilizes the recently discovered chiral domain walls, which exhibit asymmetry in their speed with respect to magnetic fields. Because of this asymmetry, an alternating magnetic field results in the coherent motion of the domain walls in one direction. Such coherent unidirectional motion is achieved even for an array of magnetic bubble domains, enabling the design of a new device prototype—magnetic bubblecade memory—with two-dimensional data-storage capability.

Editorial 25/1: 25 years of electronic markets

Dear readers of Electronic Markets,With this issue, Electronic Markets enters its 25th year ofpublication.Ithasbeenanimpressivejourneyfromasix-pagenewsletter published in German to a full-scale internationalacademic journal listed in the Social Sciences Citation Index(SSCI). This quarter century anniversary provides an oppor-tunity to look back on the various stages of ElectronicMarkets. As shown in Fig. 1, the journal was founded as anewsletter of a research project called “Competence CenterElectronic Markets” (CC EM) at the University of St. Gallenin Switzerland. Based on prior publications, in particular theseminal article on electronic markets and hierarchies byMalone et al. (1987), CC EM created a platform funded byseveral companiestoinvestigatethephenomenonofelectron-ic markets, which was still in its infancy. The diffusion ofinternational as well as open information and communicationtechnologies was conceived as a disruptive force that favors ashift from bilaterally hierarchical to multilateral market-likeformsofcoordinationamong businesses.Thiswaswell beforethe“E-Businesshype”andsome20yearslater,theexpectationproved true. Although empirical proof for the “move to themarket” hypothesis is still difficult, more electronic platformslinking businesses are available today than ever before. Asstated in the review article on “Twenty years of electronicmarkets research” (Alt and Klein 2011,p.44)an“extensionof market coordination into a broad and diverse array of do-mains from marketing, to health care or forecasting” tookplace.The“EMnewsletter”alsoexperiencedaquickevolutionasalready two years later it comprised a total of 32 pages, all ofthem in English. Then in 1996 the first step towards a moreprofessional journal was taken and the publishing companyvdf of the Swiss Federal Institute of Technology in Zurichpresented the former newsletter in a new layout (see Fig. 1)and also in a quarterly cycle. After eight issues, Routledge—now part of Taylor & Francis Group—led the journal to in-creaseitsinternationalvisibilityandalsointroducedadouble-blindpeerreviewprocess.Alongtheselines,eightissueswerepublished and Electronic Markets was established as a trulyacademicjournalwithaninternationaleditorialboard.In2009another change occurred and Springer became the publishingcompanyofElectronicMarkets.Thiscoincidedwiththehand-over of the Editor-in-Chief position from Beat Schmid toHubert Osterle, who were both long-serving professors atthe University of St. Gallen.During all those years, the Editorial Team of ElectronicMarkets constantly changed as well. In particular, this refersto the position of the Executive Editor, which was usually heldby young researchers, who left after a few years to finish theirPhD. While this position has seen some fluctuation, ElectronicMarkets has also experienced stability, as our now Editors-in-Chief,RainerAltandHans-DieterZimmermannhavebeenpartof the Editorial Team for many years. Figure 2 provides asnapshotonhowtheentireteam,includingthepublishers,haveevolved since 1991. It shows several milestones and that manycolleagues have participated in shaping Electronic Markets tobecome what it is today. Among the key achievements are:– Ranking. With the inclusion of Electronic Markets in theSSCI, an impact factor (IF) was calculated, which manyrecognize as a kind of“gold standard” in scientific

Friction behaviour of TiAlN films around cubic/hexagonal transition: A 2D grazing incidence X-ray diffraction and electron energy loss spectroscopy study

The properties at different scales of Ti1−xAlxN films deposited by reactive magnetron sputtering from TiAl sintered (S) targets produced by powder metallurgy are compared with those of a set of films previously deposited in the same conditions from mosaic targets (M) made of pure Ti and Al metals. For compositions close to the hcp/fcc transition (around x=0.6), the friction behaviour, growth directions and organization of crystallized domains are found to be sensitive to the type of target used. The resistance to crack creation is higher for Ti0.54Al0.46N (S) and Ti0.38Al0.62N (S) than for Ti0.50Al0.50N (M) and Ti0.32Al0.68N (M). From the measurement of mechanical properties, toughness, and wear volumes and from the observation of wear tracks, it is found that films prepared from sintered targets exhibit a better wear resistance. Grazing incidence X-ray diffraction and electron energy loss spectroscopy in Transmission Electronic Microscopy are used to investigate the long- and short-range orders within the films. The morphology of Ti0.54Al0.46N (S) film can be considered as an array of crystalline domains having reciprocal-space vectors 111 and 200 directed along the meridian but with random in-plane orientation. Ti0.38Al0.62N (S) Al-rich film presents a random orientation of the crystalline domains whereas Ti0.32Al0.68N (M) deposited from composite targets exhibits a well-oriented fibrillar structure. The N K-edge Electron Energy Loss Near Edge Spectra are discussed with previous results of Extended X-ray Absorption Fine Structure Spectroscopy, which has evidenced different values of Al–N and Ti–N bond lengths, either octahedral (cubic-like) or tetrahedral (hexagonal-like) within Ti0.50Al0.50N (M) and Ti0.32Al0.68N (M) films. For similar compositions, films deposited from sintered alloys contain more nitrogen atoms in octahedral cubic-like environment than coatings made from mosaic targets, which could explain their better resistance to cracking, higher hardness and better wear resistance.

Exploring remote earthquake triggering potential across EarthScopes' Transportable Array through frequency domain array visualization

AbstractTo better understand earthquake source processes involved in dynamically triggering remote aftershocks, we use data from the EarthScope Transportable Array (TA) that provide uniform station sampling, similar recording capabilities, large spatial coverage, and, in many cases, repeat sampling at each site. To avoid spurious detections, which are an inevitable part of automated time domain amplitude threshold detection methods, we develop a frequency domain earthquake detection algorithm that identifies coherent signal patterns through array visualization. This method is tractable for large data sets, ensures robust catalogs, and delivers higher resolution observations than what are available in current catalogs. We explore seismicity rate changes local to the TA stations following 18 global main shocks (M ≥ 7) that generate median peak dynamic stress amplitudes of 0.001–0.028 MPa across the array. From these main shocks, we find no evidence of prolific or widespread remote dynamic triggering in the continental U.S. within the main shock's wave train or following main shock stress transients within 2 days. However, limited evidence for rate increases exist in localized source regions. These results suggest that for these data, prolific, remote earthquake triggering is a rare phenomenon throughout a wide range of observable magnitudes. We further conclude that within the lower range of previously reported triggering thresholds, surface wave amplitude does not correlate well with observed cases of dynamic triggering. We propose that other characteristics of the triggering wavefield, in addition to specific conditions at the site, will drive the occurrence of triggering at these amplitudes.

Acoustical transduction in two-dimensional piezoelectric array

The acoustical transduction in an array of ferroelectric domains with alternating piezoelectric coefficients is characterized by multi-frequency resonances, which occur at the boundary of the acoustic Brillouin zone (ABZ). The resonances correspond to two successive domain excitations in the first and second ABZ correspondingly, where the speed of ultrasound is somewhat different. An important parameter for acoustical transduction is the electric impedance Z. The results of the theoretical and experimental investigations of Z in a periodically poled LiNbO3 are presented. The magnitude and phase of Z depend on the array parameters including domain resonance frequency and domain number; Z of arrays consisting of up to 88 0.45-mm-long domains in the zx-cut crystal are investigated. The strong changes in Z-magnitude and phase are observed in the range of 3–4 MHz. The two resonance zones are within 3.33 ± 0.05 MHz and 3.67± 0.05 MHz. The change in domain number influences Z and its phase. By varying the number of inversely poled domains and resonance frequencies, one can significantly control/change the electrical impedance of the multidomain array. The findings may be used for developing new acoustic sensors and transducers.

Steganalysis of images based on spatial domain and two-dimensional JPEG array

The aim of digital image steganalysis is to detect hidden information (which can be a message or an image) in a steganographic image. An ideal steganography method encrypts the information in the image such that it cannot be easily detected. Currently, a wide variety of different steganography techniques are being used; therefore, more advanced steganalysis methods are needed that can detect the steganographic images coded by different techniques. A typical steganalysis technique consists of two parts: (1) feature extraction and (2) classification. In this paper, a new steganalysis technique based on the Markov chain process is proposed. In the proposed technique, after extraction of the new features, a non-linear classifier named support vector machine is applied to classify clean and encrypted images. Analysis of variance is used to reduce the dimensions of the proposed features. The performance of the proposed technique is compared against subtractive DCT coefficient adjacency matrix (SDAM) and subtractive pixel adjacency matrix (SPAM) methods using an image database prepared by three strong steganography techniques called yet another steganographic scheme, model based, and perturbed quantization. The obtained results show that the proposed method provides better performance than SDAM and SPAM methods.

Identifying key domains of health-related quality of life for patients with chronic obstructive pulmonary disease: the patient perspective.

BackgroundNumerous instruments are available to measure health-related quality of life (HRQoL) in patients with Chronic Obstructive Pulmonary Disease (COPD), covering a wide array of domains ranging from symptoms such as dyspnea, cough and wheezing, to social and emotional functioning. Currently no information or guide is available yet to aid the selection of domains for a particular study or disease population. The aim of this paper is to identify which domains of HRQoL are most important with respect to COPD, from the patient perspective.MethodsTwenty-one Dutch patients with COPD were asked to describe important domains impacted by COPD freely; second, they were presented with cues (domains from the Patient-Reported Outcomes Measurement Information System (PROMIS) framework) and were asked to select the domains that were most relevant to them. During the interview, the patients were asked to indicate in which way the selected domains impact their lives. Both the answers to the open question, and the patient statements motivating nomination of PROMIS domains were coded into themes.ResultsThe most relevant (sub)domains of HRQoL for patients with COPD were: physical health (fatigue, physical functioning), social health (instrumental support, ability to participate in social roles and activities, companionship, and emotional support), and coping with COPD.ConclusionWe identified which domains of HRQoL are most important to patients with COPD. One of these (coping with COPD) is not explicitly covered by PROMIS, or by traditional questionnaires that are used to measure HRQoL in COPD.

Hydrophobicity of electron beam modified surface of hydroxyapatite films

Arrays of micron-sized domains of modified surface potential were created on hydroxyapatite films by mid-energy (20keV) electron beam irradiation available in a laboratory scanning electron microscope. The dosage of electron beam was varied between 10−3 and 103μC/cm2 to inject charge into the film surface. Contrary to the conventional electrowetting theory, the dosage of injected charge used in creating such microdomains caused a gradual increase of the water contact angle from 57° to 93° due to the elimination of the polar component of the surface free energy. Surface contamination by carbonaceous species can be held only partially responsible for such behavior at lower dosage of electron beam. A transfer of free surface charge to water and an electron beam induced disruption of polar orientation of OH ions have been attributed to be influencial factors in the overall dewetting behavior.

Cerebellar zonal patterning relies on Purkinje cell neurotransmission.

Cerebellar circuits are patterned into an array of topographic parasagittal domains called zones. The proper connectivity of zones is critical for motor coordination and motor learning, and in several neurological diseases cerebellar circuits degenerate in zonal patterns. Despite recent advances in understanding zone function, we still have a limited understanding of how zones are formed. Here, we focused our attention on Purkinje cells to gain a better understanding of their specific role in establishing zonal circuits. We used conditional mouse genetics to test the hypothesis that Purkinje cell neurotransmission is essential for refining prefunctional developmental zones into sharp functional zones. Our results show that inhibitory synaptic transmission in Purkinje cells is necessary for the precise patterning of Purkinje cell zones and the topographic targeting of mossy fiber afferents. As expected, blocking Purkinje cell neurotransmission caused ataxia. Using in vivo electrophysiology, we demonstrate that loss of Purkinje cell communication altered the firing rate and pattern of their target cerebellar nuclear neurons. Analysis of Purkinje cell complex spike firing revealed that feedback in the cerebellar nuclei to inferior olive to Purkinje cell loop is obstructed. Loss of Purkinje neurotransmission also caused ectopic zonal expression of tyrosine hydroxylase, which is only expressed in adult Purkinje cells when calcium is dysregulated and if excitability is altered. Our results suggest that Purkinje cell inhibitory neurotransmission establishes the functional circuitry of the cerebellum by patterning the molecular zones, fine-tuning afferent circuitry, and shaping neuronal activity.

Bergmann Glia are Patterned into Topographic Molecular Zones in the Developing and Adult Mouse Cerebellum.

Cerebellar circuits are patterned into an array of topographic parasagittal domains called zones. Zones are best revealed by gene expression, circuit anatomy, and cellular degeneration patterns. Thus far, the study of zones has been focused heavily on how neurons are organized. Because of this, detailed neuronal patterning maps have been established for Purkinje cells, granule cells, Golgi cells, unipolar brush cells, and also for the terminal field organization of climbing fiber and mossy fiber afferents. In comparison, however, it remains poorly understood if glial cells are also organized into zones. We have identified an Npy-Gfp BAC transgenic mouse line (Tau-Sapphire Green fluorescent protein (Gfp) is under the control of the neuropeptide Y (Npy) gene regulatory elements) that can be used to label Bergmann glial cells with Golgi-like resolution. In these adult transgenic mice, we found that Npy-Gfp expression was localized to Bergmann glia mainly in lobules VI/VII and IX/X. Using double immunofluorescence, we show that in these lobules, Npy-Gfp expression in the Bergmann glia overlaps with the pattern of the small heat shock protein HSP25, a Purkinje cell marker for zones located in lobules VI/VII and IX/X. Developmental analysis starting from the day of birth showed that HSP25 and Npy-Gfp expression follow a similar program of spatial and temporal patterning. However, loss of Npy signaling did not alter the patterning of Purkinje cell zones. We conclude that Bergmann glial cells are zonally organized and their patterns are restricted by boundaries that also confine cerebellar neurons into a topographic circuit map.

X-ray diffraction studies of stripelike ferroelectric domains in thin films of BiFeO3

We have used x-ray diffraction to study the structure of strained, epitaxial ${\text{BiFeO}}_{3}$ (BFO) films, which exhibit ordered arrays of stripelike ferroelectric domains, in which the polarization vector P alternates by either 109${}^{\ensuremath{\circ}}$ or 71${}^{\ensuremath{\circ}}$. Diffraction maps exhibit an intricate satellite structure that arises from coherent, gratinglike diffraction from the domain structure. In the case of the 109${}^{\ensuremath{\circ}}$ arrays, the domain structure was found to exert a strain modulation on the ${\text{DyScO}}_{3}$ substrate, with the same periodicity, indicating that domains in BFO can have an influence on the substrate structure. In the case of the 71${}^{\ensuremath{\circ}}$ arrays, in which there is no contrast between neighboring domains and coherent scattering is not expected, weak scattering is nonetheless observed, which we interpret as evidence for previously unobserved, internal strains in these domain walls. To understand the x-ray data, we introduce a simple, single-scattering model that incorporates Gaussian disorder and fits the diffraction maps, providing domain periods and surface ``puckering'' angles that are in good agreement with atomic force microscopy and piezoresponse force microscopy measurements. Our study demonstrates a simple, computationally inexpensive technique for semiquantitatively interpreting coherent domain scattering in ferroelectric films, and suggests that tuning domain structures is a potential route to engineering the near-surface properties of perovskite oxides.

The Many Faces of Lipid Rafts

The Many Faces of Lipid Rafts

Longitudinal course of cognitive deficits in bipolar disorder: A meta-analytic study

ObjectivePersistent cognitive deficits in bipolar disorder represent a major impediment to functional adjustment, but their static or progressive nature remains to be ascertained. The aim of this study was to synthesize findings from longitudinal research in order to examine the trajectory of cognitive impairment in bipolar disorder. MethodA literature search was conducted through online databases covering the period between January 1990 and February 2014. Two approaches were undertaken. First, the results of longitudinal studies including neuropsychological assessment of stable bipolar patients at baseline and after a follow-up period of at least one year were meta-analyzed so as to obtain overall test–retest effect sizes for neurocognitive domains. Second, meta-analysis was restricted to longitudinal studies of bipolar patients including a control group. Patients’ and controls’ overall test–retest effect sizes were compared. ResultsBipolar patients’ performance on 14 cognitive measures remained stable after a mean follow-up period of 4.62 years. When meta-analysis was restricted to controlled studies, no patient-control differences were found regarding longitudinal cognitive outcomes. LimitationsTest–retest differences for medication variables and mood state could not be controlled. Sufficient data were not available to investigate a wider array of neuropsychological domains. Furthermore, most primary studies included relatively short test–restest intervals. ConclusionTo date, the available evidence from longitudinal studies is not in accordance with the hypothesis of a progressive nature of cognitive deficits in BD. The implications of this finding for further research are discussed.

Dynamically-tunable colloidal band-pass and band-gap filters

We theoretically study particle motion on a periodic array of positive and negative magnetization domains having non-equal widths driven by a multi-frequency magnetic field input signal. Colloidal particles move across the substrate with positive, zero, or negative time-averaged velocity depending on the frequency ratio, the phase difference, and the ratio of the external field strength to the substrate magnetization. Simulations show that particles of a certain size range can either be transported or locally trapped, thereby providing a mechanism for implementing tunable colloidal band-pass and colloidal band-gap filters.

Methyllysine Reader Plant Homeodomain (PHD) Finger Protein 20-like 1 (PHF20L1) Antagonizes DNA (Cytosine-5) Methyltransferase 1 (DNMT1) Proteasomal Degradation

Inheritance of DNA cytosine methylation pattern during successive cell division is mediated by maintenance DNA (cytosine-5) methyltransferase 1 (DNMT1). Lysine 142 of DNMT1 is methylated by the SET domain containing lysine methyltransferase 7 (SET7), leading to its degradation by proteasome. Here we show that PHD finger protein 20-like 1 (PHF20L1) regulates DNMT1 turnover in mammalian cells. Malignant brain tumor (MBT) domain of PHF20L1 binds to monomethylated lysine 142 on DNMT1 (DNMT1K142me1) and colocalizes at the perinucleolar space in a SET7-dependent manner. PHF20L1 knockdown by siRNA resulted in decreased amounts of DNMT1 on chromatin. Ubiquitination of DNMT1K142me1 was abolished by overexpression of PHF20L1, suggesting that its binding may block proteasomal degradation of DNMT1K142me1. Conversely, siRNA-mediated knockdown of PHF20L1 or incubation of a small molecule MBT domain binding inhibitor in cultured cells accelerated the proteasomal degradation of DNMT1. These results demonstrate that the MBT domain of PHF20L1 reads and controls enzyme levels of methylated DNMT1 in cells, thus representing a novel antagonist of DNMT1 degradation.

Ubiquitin code assembly and disassembly

Ubiquitin, a 76 amino-acid polypeptide, presents a compact three-dimensional structure, utilising a fold that recurs within larger polypeptides and in other protein modifiers, such as NEDD8 and SUMO. Ubiquitylation was initially recognised as a signal for proteasome-mediated degradation. We shall consider here how this view has evolved to appreciate that the dynamic appendage of different types of ubiquitin chains represents a versatile, three-dimensional code, fundamental to the control of many cellular processes.

Predictors of quality of life in people with Parkinson’s disease: evidence for both domain specific and general relationships

Purpose: To assess the determinants of health-related quality of life (HrQoL) in people with Parkinson’s disease (PD). Method: Eighty-one people with a diagnosis of idiopathic PD took part in a cross-sectional questionnaire-based study. Measures were collected in a community setting and included established determinants of HrQoL (demographic, clinical and cognitive variables) but also included a wide range of mental health variables (depression, anxiety and stress) and, for the first time, positive psychological functioning (optimism and self-esteem). HrQoL was measured by the full version of the Parkinson’s Disease Questionnaire (PDQ-39) which includes eight domains of functioning. Results: Mental health measures (depression, anxiety and stress) were more influential than any other block of determinants and influenced a broader array of HrQoL domains including physical ones. There was some evidence of domain-specific relationships, e.g. between physical determinants and the more physically-oriented HrQoL domains, and between mental health determinants and emotional well-being. However, cognitive ability did not influence the HrQoL domain of cognitive impairment. Conclusions: The contribution of a multi-disciplinary approach is crucial given the many variables which affect HrQoL; in particular, significant overall improvements on HrQoL are unlikely if only physical rehabilitation is offered. Rehabilitation is likely to be beneficial in terms of HrQoL only if it is planned and delivered holistically.Implications for RehabilitationInterventions to improve physical function may have only limited impact on quality of life and might be limited to more physical HrQoL domains.Psychological interventions have the potential to improve quality of life over a wider range of both emotional and physical HrQoL domains.Clinician-measured level of functioning does not necessarily translate into patient-perceived levels of functional ability and relatively small objective decreases in ability can be appraised much more significantly disabling by people with PD.