The Three-Dimensional Structure of Aspergillus niger Pectin Lyase B at 1.7-Å Resolution1

The three-dimensional structure of Aspergillus niger pectin lyase B (PLB) has been determined by crystallographic techniques at a resolution of 1.7 Å. The model, with all 359 amino acids and 339 water molecules, refines to a final crystallographic R factor of 16.5%. The polypeptide backbone folds into a large right-handed cylinder, termed a parallel β helix. Loops of various sizes and conformations protrude from the central helix and probably confer function. The largest loop of 53 residues folds into a small domain consisting of three antiparallel β strands, one turn of an α helix, and one turn of a 310 helix. By comparison with the structure of Erwinia chrysanthemi pectate lyase C (PelC), the primary sequence alignment between the pectate and pectin lyase subfamilies has been corrected and the active site region for the pectin lyases deduced. The substrate-binding site in PLB is considerably less hydrophilic than the comparable PelC region and consists of an extensive network of highly conserved Trp and His residues. The PLB structure provides an atomic explanation for the lack of a catalytic requirement for Ca2+ in the pectin lyase family, in contrast to that found in the pectate lyase enzymes. Surprisingly, however, the PLB site analogous to the Ca2+ site in PelC is filled with a positive charge provided by a conserved Arg in the pectin lyases. The significance of the finding with regard to the enzymatic mechanism is discussed.

Retro and retroenantio analogs of cecropin-melittin hybrids.

Hybrid analogs of cecropin A (CA) and melittin (M), which are potent antibacterial peptides, have been synthesized. To understand the structural requirements for this antibacterial activity, we have also synthesized the enantio, retro, and retroenantio isomers of two of the hybrids and their N-terminally acetylated derivatives. All analogs of CA(1-13)M(1-13)-NH2 were as active as the parent peptide against five test bacterial strains, but one bacterial strain was resistant to the retro and retroenantio derivatives. Similarly, all analogs of CA(1-7)M(2-9)-NH2 were active against four strains, while two strains were resistant to the retro and retroenantio analogs containing free NH3+ end groups, but acetylation restored activity against one of them. From these data it was concluded that chirality of the peptide was not a critical feature, and full activity could be achieved with peptides containing either all L- or all D-amino acids in their respective right-handed or left-handed helical conformations. For most of the bacterial strains, the sequence of these peptides or the direction of the peptide bonds could be critical but not both at the same time. For some strains, both needed to be conserved.

V. Child's leather glove, ca. 1900s

This series contains one right-handed, child-sized leather glove with a snap button labeled "Meyers Make." The glove's seams have hand-sewn embroidery with red and orange thread. The glove was found in the pocket of the embroidered pocketbook and the items are housed together in HUM 96 Box 1.

Development of a magnetic resonance compatible wrist device for the analysis of movement encoding in the brain

Tese de mestrado integrado em Engenharia Biomédica e Biofísica, apresentada à Universidade de Lisboa, através da Faculdade de Ciências, 2016

Radiomic Texture Analysis Mapping Predicts Areas of True Functional MRI Activity.

Individual analysis of functional Magnetic Resonance Imaging (fMRI) scans requires user-adjustment of the statistical threshold in order to maximize true functional activity and eliminate false positives. In this study, we propose a novel technique that uses radiomic texture analysis (TA) features associated with heterogeneity to predict areas of true functional activity. Scans of 15 right-handed healthy volunteers were analyzed using SPM8. The resulting functional maps were thresholded to optimize visualization of language areas, resulting in 116 regions of interests (ROIs). A board-certified neuroradiologist classified different ROIs into Expected (E) and Non-Expected (NE) based on their anatomical locations. TA was performed using the mean Echo-Planner Imaging (EPI) volume, and 20 rotation-invariant texture features were obtained for each ROI. Using forward stepwise logistic regression, we built a predictive model that discriminated between E and NE areas of functional activity, with a cross-validation AUC and success rate of 79.84% and 80.19% respectively (specificity/sensitivity of 78.34%/82.61%). This study found that radiomic TA of fMRI scans may allow for determination of areas of true functional activity, and thus eliminate clinician bias.

The mismatch negativity (MMN) response to complex tones and spoken words in individuals with aphasia

Background: The mismatch negativity (MMN) is a fronto-centrally distributed event-related potential (ERP) that is elicited by any discriminable auditory change. It is an ideal neurophysiological tool for measuring the auditory processing skills of individuals with aphasia because it can be elicited even in the absence of attention. Previous MMN studies have shown that acoustic processing of tone or pitch deviance is relatively preserved in aphasia, whereas the basic acoustic processing of speech stimuli can be impaired (e.g., auditory discrimination). However, no MMN study has yet investigated the higher levels of auditory processing, such as language-specific phonological and/or lexical processing, in individuals with aphasia. Aims: The aim of the current study was to investigate the MMN response of normal and language-disordered subjects to tone stimuli and speech stimuli that incorporate the basic auditory processing (acoustic, acoustic-phonetic) levels of non-speech and speech sound processing, and also the language-specific phonological and lexical levels of spoken word processing. Furthermore, this study aimed to correlate the aphasic MMN data with language performance on a variety of tasks specifically targeted at the different levels of spoken word processing. Methods M Procedures: Six adults with aphasia (71.7 years +/- 3.0) and six healthy age-, gender-, and education-matched controls (72.2 years +/- 5.4) participated in the study. All subjects were right-handed and native speakers of English. Each subject was presented with complex harmonic tone stimuli, differing in pitch or duration, and consonant-vowel (CV) speech stimuli (non-word /de:/versus real world/deI/). The probability of the deviant for each tone or speech contrast was 10%. The subjects were also presented with the same stimuli in behavioural discrimination tasks, and were administered a language assessment battery to measure their auditory comprehension skills. Outcomes O Results: The aphasic subjects demonstrated attenuated MMN responses to complex tone duration deviance and to speech stimuli (words and non-words), and their responses to the frequency, duration, and real word deviant stimuli were found to strongly correlate with performance on the auditory comprehension section of the Western Aphasia Battery (WAB). Furthermore, deficits in attentional lexical decision skills demonstrated by the aphasic subjects correlated with a word-related enhancement demonstrated during the automatic MMN paradigm, providing evidence to support the word advantage effect, thought to reflect the activation of language-specific memory traces in the brain for words. Conclusions: These results indicate that the MMN may be used as a technique for investigating general and more specific auditory comprehension skills of individuals with aphasia, using speech and/or non-speech stimuli, independent of the individual's attention. The combined use of the objective MMN technique and current clinical language assessments may result in improved rehabilitative management of aphasic individuals.

The acute effects of mild traumatic brain injury on finger tapping with and without word repetition

This study aimed to investigate the acute effects of mild Traumatic Brain Injury (mTBI) on the performance of a finger tapping and word repetition dual task in order to determine working memory impairment in mTBI Sixty-four (50 male, 14 female) right-handed cases of mTBI and 26 (18 male and 8 female) right-handed cases of orthopaedic injuries were tested within 24 hours of injury. Patients with mTBI completed fewer correct taps in 10 seconds than patients with orthopaedic injuries, and female mTBI cases repeated fewer words. The size of the dual task decrement did not vary between groups. When added to a test battery including the Rapid Screen of Concussion (RSC; Comerford, Geffen, May, Medland T Geffen, 2002) and the Digit Symbol Substitution Test,finger tapping speed accounted for 1% of between groups variance and did not improve classification rates of male participants. While the addition of tapping rate did not improve the sensitivity and specificity of the RSC and DSST to mTBI in males, univariate analysis of motor performance in females indicated. that dual task performance might be diagnostic. An increase in female sample Size is warranted. These results confirm the view that there is a generalized slowing of processing ability following mTBI.

Distortion product otoacoustic emissions in school children: Effects to gender, ear asymmetry and handedness

Accurate interpretation of distortion product otoacoustic emission (DPOAE) data cannot be made without realizing the effects of non-pathological factors on DPOAEs. The present study aimed to examine the effects of ear asymmetry, gender and handedness on DPOAEs obtained from school children. One thousand and three children (528 boys and 475 girls) with a mean age of 6.2 years (SD = 0.4, range = 5.2 7.9 years) were tested in a quiet room at their schools using the GSI-60 DPOAE system. The stimuli consisted of two pure tones of different frequencies f1 and f2 presented at 65 and 55dB SPL respectively. A DP-gram was obtained for each ear with f2 varying from 1.1 to 6.0 kHz and the ratio of f2/f1 being kept at 1.21. The signal-to-noise ratios (SNR) (DPOAE amplitude minus the mean noise floor) at the tested frequencies 1.1, 1.5, 1.9, 2.4, 3.0, 3.8, 4.8, and 6.0 kHz were measured. The results revealed a small, but significant difference in SNR between ears, with right ears showing a higher mean SNR than left ears at 1.9, 3.0, 3.8 and 6.0 kHz. At these frequencies, the difference in mean SNR between ears was less than 1 dB. A significant gender effect was also found, with girls exhibiting a higher SNR than boys at 3.8, 4.8 and 6.0 kHz. The difference in mean SNR, as a result of the gender effect, was about 1 to 2 dB at these frequencies. The results from the present study indicated no significant difference in mean SNR between left-handed and right-handed children for all tested frequencies. In conclusion, these non-pathological characteristics of DPOAEs should be considered in the interpretation of DPOAE results for school children.

PCSK6 is associated with handedness in individuals with dyslexia

Approximately 90% of humans are right-handed. Handedness is a heritable trait, yet the genetic basis is not well understood. Here we report a genome-wide association study for a quantitative measure of relative hand skill in individuals with dyslexia [reading disability (RD)]. The most highly associated marker, rs11855415 (P = 4.7 × 10-7), is located within PCSK6. Two independent cohorts with RD show the same trend, with the minor allele conferring greater relative right-hand skill. Meta-analysis of all three RD samples is genome-wide significant (n = 744, P = 2.0 × 10-8). Conversely, in the general population (n = 2666), we observe a trend towards reduced laterality of hand skill for the minor allele (P = 0.0020). These results provide molecular evidence that cerebral asymmetry and dyslexia are linked. Furthermore, PCSK6 is a protease that cleaves the left–right axis determining protein NODAL. Functional studies of PCSK6 promise insights into mechanisms underlying cerebral lateralization and dyslexia.

Activation of the left inferior frontal gyrus in the first 200 ms of reading:evidence from magnetoencephalography (MEG)

Background - It is well established that the left inferior frontal gyrus plays a key role in the cerebral cortical network that supports reading and visual word recognition. Less clear is when in time this contribution begins. We used magnetoencephalography (MEG), which has both good spatial and excellent temporal resolution, to address this question. Methodology/Principal Findings - MEG data were recorded during a passive viewing paradigm, chosen to emphasize the stimulus-driven component of the cortical response, in which right-handed participants were presented words, consonant strings, and unfamiliar faces to central vision. Time-frequency analyses showed a left-lateralized inferior frontal gyrus (pars opercularis) response to words between 100–250 ms in the beta frequency band that was significantly stronger than the response to consonant strings or faces. The left inferior frontal gyrus response to words peaked at ~130 ms. This response was significantly later in time than the left middle occipital gyrus, which peaked at ~115 ms, but not significantly different from the peak response in the left mid fusiform gyrus, which peaked at ~140 ms, at a location coincident with the fMRI–defined visual word form area (VWFA). Significant responses were also detected to words in other parts of the reading network, including the anterior middle temporal gyrus, the left posterior middle temporal gyrus, the angular and supramarginal gyri, and the left superior temporal gyrus. Conclusions/Significance - These findings suggest very early interactions between the vision and language domains during visual word recognition, with speech motor areas being activated at the same time as the orthographic word-form is being resolved within the fusiform gyrus. This challenges the conventional view of a temporally serial processing sequence for visual word recognition in which letter forms are initially decoded, interact with their phonological and semantic representations, and only then gain access to a speech code.

Gender differences in the sensitivity to negative stimuli:cross-modal affective priming study

Background: There is evidence showing that men and women differ with regard to the processing of emotional information. However, the mechanisms behind these differences are not fully understood. Method: The sample comprised of 275 (167 female) right-handed, healthy participants, recruited from the community. We employed a customized affective priming task, which consisted of three subtests, differing in the modality of the prime (face, written word, and sound). The targets were always written words of either positive or negative valence. The priming effect was measured as reaction time facilitation in conditions where both prime and target were emotional (of the same positive or negative valence) compared with conditions where the emotional targets were preceded by neutral primes. Results: The priming effect was observed across all three modalities, with an interaction of gender by valence: the priming effect in the emotionally negative condition in male participants was stronger compared with females. This was accounted for by the differential priming effect within the female group where priming was significantly smaller in the emotionally negative conditions compared with the positive conditions. The male participants revealed a comparable priming effect across both the emotionally negative and positive conditions. Conclusion: Reduced priming in negative conditions in women may reflect interference processes due to greater sensitivity to negative valence of stimuli. This in turn could underlie the gender-related differences in susceptibility to emotional disorders.

Ocular dominance and handedness in golf putting

Purpose: In golf, the impact of eye-hand dominance on putting performance has long been debated. Eye-hand dominance is thought to impact how golfers judge the alignment of the ball with the target and the club with the ball, as well as how golfers visualize the line of the putt when making decisions about the force needed to hit the ball. Previous studies have all measured ocular dominance in primary gaze only, despite golfers spending a significant amount of their time in a putting stance (bent at the hips, head tilted down). Thus, the purpose of this study was to assess ocular dominance in both primary gaze (aligning the ball with the target) and putting gaze (addressing the ball and aligning the club). Methods: This study investigatedmeasuring pointing oculardominance in both primary and putting gaze positions on 31 golfers (14 amateur, 7 club professionals, and 10 top professionals). All playerswere right-handed golfers, although one reported having no hand dominance and one reported being strongly left hand dominant. Results: The results showed that (1) primary and putting gaze ocular dominances are not equal, nor are they predictive of each other; (2) themagnitude of putting ocular dominance is significantly less than themagnitude of primary gaze ocular dominance; (3) ocular dominance is not correlated with handedness in either primary or putting gaze; and (4) eye-hand dominance is not associated with increased putting skill, although ocular dominance may be associated with increased putting success. Conclusions: It is important that coaches assess golfers' ocular dominance in both primary and putting gaze positions to ensure they have the most accurate information upon which to base their vision strategy decisions.

What one hand giveth the other taketh away:some unpredicted effects of enantiomers in psychopharmacology

It is well known that many medicines are a mixture of two enantiomers, or mirror-image molecules. Two enantiomers occur when a molecule has a single chiral centre and the two mirror images, called S or L (left handed) and R or D (right handed), are usually found in equal amounts in the parent (racemic) mixture. While for many compounds used in clinical practice the active moiety is found in one of the two enantiomers with the other being seen as an unnecessary and redundant component of the racemic mixture, the difference between enantiomers can mean a difference between therapeutic and adverse effects, as well as in beneficial pharmacological effect and potency. © 2010 The Author(s).

Binding of small molecules to DNA junctions

Previous results in our laboratory suggest that the (CG) 4 segments whether present in a right-handed or a left-handed conformation form distinctive junctions with adjacent random sequences. These junctions and their associated sequences have unique structural and thermodynamic properties that may be recognized by DNA-binding molecules. This study probes these sequences by using the following small ligands: actinomycin D, 1,4-bis(((di(aminoethyl)amino)ethyl)amino)anthracene-9,10-dione, ametantrone, and tris(phenanthroline)ruthenium (II). These ligands may recognize the distinctive features associated to the (CG)4 segment and its junctions and thus interact preferentially near these sequences. Restriction enzyme inhibition assays were used to determine whether or not binding interactions took place, and to approximate locations of these interactions. These binding studies are first carried out using two small synthetic oligomers BZ-III and BZ-IV. The (5meCG)4 segment present in BZ-III adopts the Z-conformation in the presence of 50 m M Co(NH3)63+. In BZ-IV, the unmethylated (CG)4 segment changes to a non-B conformation in the presence of 50 m M Co(NH3)63+. BZ-IV, containing the (CG)4 segment, was inserted into a clone plasmid then digested with the restriction enzyme Hinf I to produce a larger fragment that contains the (CG)4 segment. The results obtained on the small oligomers and on the larger fragment for restriction enzyme Mbo I indicate that 1,4-bis(((di(aminoethyl)amino)ethyl)amino)anthracene-9,10-dione binds more efficiently at or near the (CG)4 segment. Restriction enzymes EcoRV, Sac I and Not I with cleavage sites upstream and downstream of the (CG)4 insert were used to further localize binding interactions in the vicinity of the (CG)4 insert. RNA polymerase activity was studied in a plasmid which contained the (CG)4 insert downstream from the promoter sites of SP6 and T7 RNA polymerases. Activities of these two polymerases were studied in the presence of each one of the ligands used throughout the study. Only actinomycin D and spider, which bind at or near the (CG)4 segment, alter the activities of SP6 and T7 RNA polymerases. Surprisingly, enhancement of polymerase activity was observed in the presence of very low concentrations of actinomycin D. These results suggest that the conformational features of (CG) segments may serve in regulatory functions of DNA. ^

Scotogenic model for co-bimaximal mixing

We present a scotogenic model, i.e. a one-loop neutrino mass model with dark right-handed neutrino gauge singlets and one inert dark scalar gauge doublet eta, which has symmetries that lead to co-bimaximal mixing, i.e. to an atmospheric mixing angle theta(23) = 45 degrees and to a CP-violating phase delta = +/-pi/2, while the mixing angle theta(13) remains arbitrary. The symmetries consist of softly broken lepton numbers L-alpha (alpha = e, mu, tau), a non-standard CP symmetry, and three L-2 symmetries. We indicate two possibilities for extending the model to the quark sector. Since the model has, besides eta, three scalar gauge doublets, we perform a thorough discussion of its scalar sector. We demonstrate that it can accommodate a Standard Model-like scalar with mass 125 GeV, with all the other charged and neutral scalars having much higher masses.