Time-Dependent Statistical and Correlation Properties of Neural Signals during Handwriting

To elucidate the cortical control of handwriting, we examined time-dependent statistical and correlational properties of simultaneously recorded 64-channel electroencephalograms (EEGs) and electromyograms (EMGs) of intrinsic hand muscles. We introduced a statistical method, which offered advantages compared to conventional coherence methods. In contrast to coherence methods, which operate in the frequency domain, our method enabled us to study the functional association between different neural regions in the time domain. In our experiments, subjects performed about 400 stereotypical trials during which they wrote a single character. These trials provided time-dependent EMG and EEG data capturing different handwriting epochs. The set of trials was treated as a statistical ensemble, and time-dependent correlation functions between neural signals were computed by averaging over that ensemble. We found that trial-to-trial variability of both the EMGs and EEGs was well described by a log-normal distribution with time-dependent parameters, which was clearly distinguished from the normal (Gaussian) distribution. We found strong and long-lasting EMG/EMG correlations, whereas EEG/EEG correlations, which were also quite strong, were short-lived with a characteristic correlation durations on the order of 100 ms or less. Our computations of correlation functions were restricted to the spectral range (13–30 Hz) of EEG signals where we found the strongest effects related to handwriting. Although, all subjects involved in our experiments were right-hand writers, we observed a clear symmetry between left and right motor areas: inter-channel correlations were strong if both channels were located over the left or right hemispheres, and 2–3 times weaker if the EEG channels were located over different hemispheres. Although we observed synchronized changes in the mean energies of EEG and EMG signals, we found that EEG/EMG correlations were much weaker than EEG/EEG and EMG/EMG correlations. The absence of strong correlations between EMG and EEG signals indicates that (i) a large fraction of the EEG signal includes electrical activity unrelated to low-level motor variability; (ii) neural processing of cortically-derived signals by spinal circuitry may reduce the correlation between EEG and EMG signals.     

Force Control Is Related to Low-Frequency Oscillations in Force and Surface EMG

Force variability during constant force tasks is directly related to oscillations below 0.5 Hz in force. However, it is unknown whether such oscillations exist in muscle activity. The purpose of this paper, therefore, was to determine whether oscillations below 0.5 Hz in force are evident in the activation of muscle. Fourteen young adults (21.07±2.76 years, 7 women) performed constant isometric force tasks at 5% and 30% MVC by abducting the left index finger. We recorded the force output from the index finger and surface EMG from the first dorsal interosseous (FDI) muscle and quantified the following outcomes: 1) variability of force using the SD of force; 2) power spectrum of force below 2 Hz; 3) EMG bursts; 4) power spectrum of EMG bursts below 2 Hz; and 5) power spectrum of the interference EMG from 10–300 Hz. The SD of force increased significantly from 5 to 30% MVC and this increase was significantly related to the increase in force oscillations below 0.5 Hz (R ² = 0.82). For both force levels, the power spectrum for force and EMG burst was similar and contained most of the power from 0–0.5 Hz. Force and EMG burst oscillations below 0.5 Hz were highly coherent (coherence = 0.68). The increase in force oscillations below 0.5 Hz from 5 to 30% MVC was related to an increase in EMG burst oscillations below 0.5 Hz (R ² = 0.51). Finally, there was a strong association between the increase in EMG burst oscillations below 0.5 Hz and the interference EMG from 35–60 Hz (R ² = 0.95). In conclusion, this finding demonstrates that bursting of the EMG signal contains low-frequency oscillations below 0.5 Hz, which are associated with oscillations in force below 0.5 Hz.     

Task-Dependent Intermuscular Motor Unit Synchronization between Medial and Lateral Vastii Muscles during Dynamic and Isometric Squats

Purpose

Motor unit activity is coordinated between many synergistic muscle pairs but the functional role of this coordination for the motor output is unclear. The purpose of this study was to investigate the short-term modality of coordinated motor unit activity–the synchronized discharge of individual motor units across muscles within time intervals of 5ms–for the Vastus Medialis (VM) and Lateralis (VL). Furthermore, we studied the task-dependency of intermuscular motor unit synchronization between VM and VL during static and dynamic squatting tasks to provide insight into its functional role.

Methods

Sixteen healthy male and female participants completed four tasks: Bipedal squats, single-leg squats, an isometric squat, and single-leg balance. Monopolar surface electromyography (EMG) was used to record motor unit activity of VM and VL. For each task, intermuscular motor unit synchronization was determined using a coherence analysis between the raw EMG signals of VM and VL and compared to a reference coherence calculated from two desynchronized EMG signals. The time shift between VM and VL EMG signals was estimated according to the slope of the coherence phase angle spectrum.

Results

For all tasks, except for singe-leg balance, coherence between 15–80Hz significantly exceeded the reference. The corresponding time shift between VM and VL was estimated as 4ms. Coherence between 30–60Hz was highest for the bipedal squat, followed by the single-leg squat and the isometric squat.

Conclusion

There is substantial short-term motor unit synchronization between VM and VL. Intermuscular motor unit synchronization is enhanced for contractions during dynamic activities, possibly to facilitate a more accurate control of the joint torque, and reduced during single-leg tasks that require balance control and thus, a more independent muscle function. It is proposed that the central nervous system scales the degree of intermuscular motor unit synchronization according to the requirements of the movement task at hand.     

Multimodal Floral Signals and Moth Foraging Decisions

Background

Combinations of floral traits – which operate as attractive signals to pollinators – act on multiple sensory modalities. For Manduca sexta hawkmoths, how learning modifies foraging decisions in response to those traits remains untested, and the contribution of visual and olfactory floral displays on behavior remains unclear.

Methodology/Principal Findings

Using M. sexta and the floral traits of two important nectar resources in southwestern USA, Datura wrightii and Agave palmeri, we examined the relative importance of olfactory and visual signals. Natural visual and olfactory cues from D. wrightii and A. palmeri flowers permits testing the cues at their native intensities and composition – a contrast to many studies that have used artificial stimuli (essential oils, single odorants) that are less ecologically relevant. Results from a series of two-choice assays where the olfactory and visual floral displays were manipulated showed that naïve hawkmoths preferred flowers displaying both olfactory and visual cues. Furthermore, experiments using A. palmeri flowers – a species that is not very attractive to hawkmoths – showed that the visual and olfactory displays did not have synergistic effects. The combination of olfactory and visual display of D. wrightii, however – a flower that is highly attractive to naïve hawkmoths – did influence the time moths spent feeding from the flowers. The importance of the olfactory and visual signals were further demonstrated in learning experiments in which experienced moths, when exposed to uncoupled floral displays, ultimately chose flowers based on the previously experienced olfactory, and not visual, signals. These moths, however, had significantly longer decision times than moths exposed to coupled floral displays.

Conclusions/Significance

These results highlight the importance of specific sensory modalities for foraging hawkmoths while also suggesting that they learn the floral displays as combinatorial signals and use the integrated floral traits from their memory traces to mediate future foraging decisions.     

A study of motor coordination and neuromuscular activities in human locomotion

By using a suitable experimental and mathematical procedure variables characterising motor coordination in human locomotion have been obtained for different subjects and correlations between them have been analysed.—1. The comparison between the EMG signals and the torques at joints point out the complex coordination of muscle activation with particular reference to the function of biarticular muscles.—1. The comparison between the EMG signals and the instantaneous length of the eleven muscles considered suggests a relevant influence of the reflex regulation from Ia afferents.—It appears that locomotion cannot be considered to be a completely stereotiped function. In fact, despite the similar kinematics, the torque time courses of different subjects present significant differences in agreement with different temporal sequence of muscle activation.     

Time course of changes in torque and neuromuscular parameters during a sustained isometric forearm flexion task to fatigue anchored to a constant rating of perceived exertion

Objective:This study examined the time course of changes in torque and electromyographic (EMG) and mechanomyographic (MMG) responses during a sustained isometric task anchored to a constant perception of exertion (RPE).Methods:Twelve college-aged men performed an isometric forearm flexion task to failure anchored to RPE=7 (OMNI-RES scale). The amplitude (AMP) and frequency (MPF) of the EMG and MMG signals from the biceps brachii were recorded. Repeated measures ANOVAs were used to examine differences for the normalized (%MVIC) torque and neuromuscular parameters.Results:The time to task failure (TTF) was 678.0±468.1s. Torque decreased significantly (p<0.001, η_p²=0.774) across time and all subjects reduced torque to zero. Post-hoc comparisons indicated that the torque values from 20–100% TTF were less than the value at 10% TTF. There were no significant (p>0.05) changes from 10–100% TTF for the EMG and MMG parameters.Conclusion:We hypothesize that RPE was maintained by various mechanisms throughout the task: group III/IV afferent neurons, adequate blood flow, and a combination of reduced contractile efficiency, collective afferent feedback (group III/IV afferents) from muscles involved with forearm flexion, and motivation that resulted in an initial decrease, plateau, and final decline in torque to zero, respectively.     

Neuromuscular Activation of the Vastus Intermedius Muscle during Isometric Hip Flexion

Although activity of the rectus femoris (RF) differs from that of the other synergists in quadriceps femoris muscle group during physical activities in humans, it has been suggested that the activation pattern of the vastus intermedius (VI) is similar to that of the RF. The purpose of present study was to examine activation of the VI during isometric hip flexion. Ten healthy men performed isometric hip flexion contractions at 25%, 50%, 75%, and 100% of maximal voluntary contraction at hip joint angles of 90°, 110° and 130°. Surface electromyography (EMG) was used to record activity of the four quadriceps femoris muscles and EMG signals were root mean square processed and normalized to EMG amplitude during an isometric knee extension with maximal voluntary contraction. The normalized EMG was significantly higher for the VI than for the vastus medialis during hip flexion at 100% of maximal voluntary contraction at hip joint angles of 110° and 130° (P < 0.05). The onset of VI activation was 230–240 ms later than the onset of RF activation during hip flexion at each hip joint angle, which was significantly later than during knee extension at 100% of maximal voluntary contraction (P < 0.05). These results suggest that the VI is activated later than the RF during hip flexion. Activity of the VI during hip flexion might contribute to stabilize the knee joint as an antagonist and might help to smooth knee joint motion, such as in the transition from hip flexion to knee extension during walking, running and pedaling.     

Effects of Perturbations to Balance on Neuromechanics of Fast Changes in Direction during Locomotion

This study investigated whether the modular control of changes in direction while running is influenced by perturbations to balance. Twenty-two healthy men performed 90° side-step unperturbed cutting manoeuvres while running (UPT) as well as manoeuvres perturbed at initial contact (PTB, 10 cm translation of a moveable force platform). Surface EMG activity from 16 muscles of the supporting limb and trunk, kinematics, and ground reaction forces were recorded. Motor modules composed by muscle weightings and their respective activation signals were extracted from the EMG signals by non-negative matrix factorization. Knee joint moments, co-contraction ratios and co-contraction indexes (hamstrings/quadriceps) and motor modules were compared between UPT and PTB. Five motor modules were enough to reconstruct UPT and PTB EMG activity (variance accounted for UPT  = 92±5%, PTB = 90±6%). Moreover, higher similarities between muscle weightings from UPT and PTB (similarity = 0.83±0.08) were observed in comparison to the similarities between the activation signals that drive the temporal properties of the motor modules (similarity = 0.71±0.18). In addition, the reconstruction of PTB EMG from fixed muscle weightings from UPT resulted in higher reconstruction quality (82±6%) when compared to reconstruction of PTB EMG from fixed activation signals from UPT (59±11%). Perturbations at initial contact reduced knee abduction moments (7%), as well as co-contraction ratio (11%) and co-contraction index (12%) shortly after the perturbation onset. These changes in co-contraction ratio and co-contraction index were caused by a reduced activation of hamstrings that was also verified in the activation signals of the specific motor module related to initial contact. Our results suggested that perturbations to balance influence modular control of cutting manoeuvres, especially the temporal properties of muscle recruitment, due to altered afferent inputs to the motor patterns. Furthermore, reduced knee stability during perturbed events may be related to overall control of lower limb muscles.     

Neuronal variability during handwriting: lognormal distribution

We examined time-dependent statistical properties of electromyographic (EMG) signals recorded from intrinsic hand muscles during handwriting. Our analysis showed that trial-to-trial neuronal variability of EMG signals is well described by the lognormal distribution clearly distinguished from the Gaussian (normal) distribution. This finding indicates that EMG formation cannot be described by a conventional model where the signal is normally distributed because it is composed by summation of many random sources. We found that the variability of temporal parameters of handwriting--handwriting duration and response time--is also well described by a lognormal distribution. Although, the exact mechanism of lognormal statistics remains an open question, the results obtained should significantly impact experimental research, theoretical modeling and bioengineering applications of motor networks. In particular, our results suggest that accounting for lognormal distribution of EMGs can improve biomimetic systems that strive to reproduce EMG signals in artificial actuators.     

Cross-frequency and iso-frequency estimation of functional corticomuscular coupling after stroke

Functional corticomuscular coupling (FCMC) between the brain and muscles has been used for motor function assessment after stroke. Two types, iso-frequency coupling (IFC) and cross-frequency coupling (CFC), are existed in sensory-motor system for healthy people. However, in stroke, only a few studies focused on IFC between electroencephalogram (EEG) and electromyogram (EMG) signals, and no CFC studies have been found. Considering the intrinsic complexity and rhythmicity of the biological system, we first used the wavelet package transformation (WPT) to decompose the EEG and EMG signals into several subsignals with different frequency bands, and then applied transfer entropy (TE) to analyze the IFC and CFC relationship between each pair-wise subsignal. In this study, eight stroke patients and eight healthy people were enrolled. Results showed that both IFC and CFC still existed in stroke patients (EEG → EMG: 1:1, 3:2, 2:1; EMG → EEG: 1:1, 2:1, 2:3, 3:1). Compared with the stroke-unaffected side and healthy controls, the stroke-affected side yielded lower alpha, beta and gamma synchronization (IFC: beta; CFC: alpha, beta and gamma). Further analysis indicated that stroke patients yielded no significant difference of the FCMC between EEG → EMG and EMG → EEG directions. Our study indicated that alpha and beta bands were essential to concentrating and maintaining the motor capacities, and provided a new insight in understanding the propagation and function in the sensory-motor system.     

Specific Muscle EMG Biofeedback for Hand Dystonia

Currently available therapies have only limited success in patients having hand dystonia (writer's cramp). We employed specific muscle EMG biofeedback (audio feedback of the EMG from proximal large muscles of the limb that show abnormally high activity during writing) in 10 of 13 consecutive patients (age, 19–62 years; all males) with a duration of illness from 6 months to 8 years. In three patients, biofeedback was not applicable due to lack of abnormal EMG values. Nine patients showed dystonic posture during writing and had hypertrophy of one or more large muscles of the dominant hand. The remaining four patients showed either involvement of small muscles or muscle wasting. Ten patients were given four or more sessions of EMG audio biofeedback from the proximal large limb muscles, which showed maximum EMG activity. They also practiced writing daily with the relaxed limb for 5 to 10 min. Nine patients showed improvement from 37 to 93% in handwriting, alleviation of discomfort, and pain (assessed on a visual analogue scale). One patient did not show any improvement. Thus EMG biofeedback improved the clinical and electromyographic picture in those patients with hand dystonia who showed EMG overactivity of proximal limb muscles during writing. This specific type of EMG biofeedback appears to be a promising tool for hand dystonia and might also be applied to other types of dystonias.     

Bilateral Deficit in Explosive Force Production Is Not Caused by Changes in Agonist Neural Drive

Bilateral deficit (BLD) describes the phenomenon of a reduction in performance during synchronous bilateral (BL) movements when compared to the sum of identical unilateral (UL) movements. Despite a large body of research investigating BLD of maximal voluntary force (MVF) there exist a paucity of research examining the BLD for explosive strength. Therefore, this study investigated the BLD in voluntary and electrically-evoked explosive isometric contractions of the knee extensors and assessed agonist and antagonist neuromuscular activation and measurement artefacts as potential mechanisms. Thirteen healthy untrained males performed a series of maximum and explosive voluntary contractions bilaterally (BL) and unilaterally (UL). UL and BL evoked twitch and octet contractions were also elicited. Two separate load cells were used to measure MVF and explosive force at 50, 100 and 150 ms after force onset. Surface EMG amplitude was measured from three superficial agonists and an antagonist. Rate of force development (RFD) and EMG were reported over consecutive 50 ms periods (0–50, 50–100 and 100–150 ms). Performance during UL contractions was compared to combined BL performance to measure BLD. Single limb performance during the BL contractions was assessed and potential measurement artefacts, including synchronisation of force onset from the two limbs, controlled for. MVF showed no BLD (P = 0.551), but there was a BLD for explosive force at 100 ms (11.2%, P = 0.007). There was a BLD in RFD 50–100 ms (14.9%, P = 0.004), but not for the other periods. Interestingly, there was a BLD in evoked force measures (6.3–9.0%, P<0.001). There was no difference in agonist or antagonist EMG for any condition (P≥0.233). Measurement artefacts contributed minimally to the observed BLD. The BLD in volitional explosive force found here could not be explained by measurement issues, or agonist and antagonist neuromuscular activation. The BLD in voluntary and evoked explosive force might indicate insufficient stabiliser muscle activation during BL explosive contractions.     

Chloroplast-avoidance response induced by high-fluence blue light in prothallial cells of the fern adiantum capillus-veneris as analyzed by microbeam irradiation

Chloroplast movement was induced by partial cell illumination using a high-fluence blue microbeam in light-grown and dark-adapted prothallial cells of the fern Adiantum capillus-veneris. Chloroplasts inside the illuminated area moved out (high-fluence response [HFR]), whereas those outside moved toward the irradiated area (low-fluence response [LFR]), although they stopped moving when they reached the border. These results indicate that both HFR and LFR signals are generated by high-fluence blue light of the same area, and that an LFR signal can be transferred long-distance from the beam spot, although an HFR signal cannot. The lifetime of the HFR signal was calculated from the traces of chloroplast movement induced by a brief pulse from a high-fluence blue microbeam to be about 6 min. This is very short compared with that of the LFR (30–40 min; T. Kagawa, M. Wada [1994] J Plant Res 107: 389–398). These data indicate that the signal transduction pathways of the HFR and the LFR must be distinct.     

Hamstring Muscle Fatigue and Central Motor Output during a Simulated Soccer Match

Purpose

To examine changes in hamstring muscle fatigue and central motor output during a 90-minute simulated soccer match, and the concomitant changes in hamstring maximal torque and rate of torque development.

Method

Eight amateur male soccer players performed a 90-minute simulated soccer match, with measures performed at the start of and every 15-minutes during each half. Maximal torque (Nm) and rate of torque development (RTD; Nm.s^–1) were calculated from maximal isometric knee flexor contractions performed at 10° of flexion. Hamstring peripheral fatigue was assessed from changes in the size and shape of the resting twitch (RT). Hamstring central motor output was quantified from voluntary activation (%) and normalized biceps femoris (BF) and medial hamstrings (MH) electromyographic amplitudes (EMG/M).

Results

Maximal torque was reduced at 45-minutes by 7.6±9.4% (p<0.05). RTD in time intervals of 0–25, 0–50, and 0–75 ms post-contraction onset were reduced after 15-minutes in the first-half between 29.6 to 46.2% (p<0.05), and were further reduced at the end of the second-half (p<0.05). Maximal EMG/M was reduced for biceps femoris only concomitant to the time-course of reductions in maximal torque (p = 0.007). The rate of EMG rise for BF and MH was reduced in early time periods (0–75 ms) post-contraction onset (p<0.05). No changes were observed for the size and shape of the RT, indicating no hamstring peripheral fatigue.

Conclusion

Centrally mediated reductions in maximal torque and rate of torque development provide insight into factors that may explain hamstring injury risk during soccer. Of particular interest were early reductions during the first-half of hamstring rate of torque development, and the decline in maximal EMG/M of biceps femoris in the latter stages of the half. These are important findings that may help explain why the hamstrings are particularly vulnerable to strain injury during soccer.     

Structure of the human RAD17–RFC clamp loader and 9–1–1 checkpoint clamp bound to a dsDNA–ssDNA junction

The RAD9–RAD1–HUS1 (9–1–1) clamp forms one half of the DNA damage checkpoint system that signals the presence of substantial regions of single-stranded DNA arising from replication fork collapse or resection of DNA double strand breaks. Loaded at the 5′-recessed end of a dsDNA–ssDNA junction by the RAD17–RFC clamp loader complex, the phosphorylated C-terminal tail of the RAD9 subunit of 9–1–1 engages with the mediator scaffold TOPBP1 which in turn activates the ATR kinase, localised through the interaction of its constitutive partner ATRIP with RPA-coated ssDNA. Using cryogenic electron microscopy (cryoEM) we have determined the structure of a complex of the human RAD17–RFC clamp loader bound to human 9–1–1, engaged with a dsDNA–ssDNA junction. The structure answers the key questions of how RAD17 confers specificity for 9–1–1 over PCNA, and how the clamp loader specifically recognises the recessed 5′ DNA end and fixes the orientation of 9–1–1 on the ssDNA.     

Multi-Proxy Temperature Reconstruction from the West Qinling Mountains,China, for the Past 500 Years

A total of 290 tree-ring samples, collected from six sites in the West Qinling Mountains of China, were used to develop six new standard tree-ring chronologies. In addition, 73 proxy records were assembled in collaboration with Chinese and international scholars, from 27 publically available proxy records and 40 tree-ring chronologies that are not available in public datasets. These records were used to reconstruct annual mean temperature variability in the West Qinling Mountains over the past 500 years (AD 1500–1995), using a modified point-by-point regression (hybrid PPR) method. The results demonstrate that the hybrid PPR method successfully integrates the temperature signals from different types of proxies, and that the method preserves a high degree of low-frequency variability. The reconstruction shows greater temperature variability in the West Qinling Mountains than has been found in previous studies. Our temperature reconstruction for this region shows: 1) five distinct cold periods, at approximately AD 1520–1535, AD 1560–1575, AD 1610–1620, AD 1850–1875 and AD 1965–1985, and four warm periods, at approximately AD 1645–1660, AD 1705–1725, AD 1785–1795 and AD 1920–1945; 2) that in this region, the 20^th century was not the warmest period of the past 500 years; and 3) that a dominant and persistent oscillation of ca. 64 years is significantly identified in the 1640–1790 period.     

An Ensemble Weighting Approach for Dendroclimatology: Drought Reconstructions for the Northeastern Tibetan Plateau

Traditional detrending methods assign equal mean value to all tree-ring series for chronology developments, despite that the mean annual growth changes in different time periods. We find that the strength of a tree-ring model can be improved by giving more weights to tree-ring series that have a stronger climate signal and less weight to series that have a weaker signal. We thus present an ensemble weighting method to mitigate these potential biases and to more accurately extract the climate signals in dendroclimatology studies. This new method has been used to develop the first annual precipitation reconstruction (previous August to current July) at the Songmingyan Mountain and to recalculate the tree-ring chronology from Shenge site in Dulan area in northeastern Tibetan Plateau (TP), a marginal area of Asian summer monsoon. The ensemble weighting method explains 31.7% of instrumental variance for the reconstructions at Songmingyan Mountain and 57.3% of the instrumental variance in the Dulan area, which are higher than those developed using traditional methods. We focus on the newly introduced reconstruction at Songmingyan Mountain, which showsextremely dry (wet) epochs from 1862–1874, 1914–1933 and 1991–1999 (1882–1905). These dry/wet epochs were also found in the marginal areas of summer monsoon and the Indian subcontinent, indicating the linkages between regional hydroclimate changes and the Indian summer monsoon.     

DNA microarrays with stem–loop DNA probes: preparation and applications

We have developed DNA microarrays containing stem–loop DNA probes with short single-stranded overhangs immobilized on a Packard HydroGel chip, a 3-dimensional porous gel substrate. Microarrays were fabricated by immobilizing self-complementary single-stranded oligonucleotides, which adopt a partially duplex structure upon denaturing and re-annealing. Hybridization of single-stranded DNA targets to such arrays is enhanced by contiguous stacking interactions with stem–loop probes and is highly sequence specific. Subsequent enzymatic ligation of the targets to the probes followed by stringent washing further enhances the mismatched base discrimination. We demonstrate here that these microarrays provide excellent specificity with signal-to-background ratios of from 10- to 300-fold. In a comparative study, we demonstrated that HydroGel arrays display 10–30 times higher hybridization signals than some solid surface DNA microarrays. Using Sanger sequencing reactions, we have also developed a method for preparing nested 3′-deletion sets from a target and evaluated the use of stem–loop DNA arrays for detecting p53 mutations in the deletion set. The stem–loop DNA array format is simple, robust and flexible in design, thus it is potentially useful in various DNA diagnostic tests.     

Predicting protein function with hierarchical phylogenetic profiles: the Gene3D Phylo-Tuner method applied to eukaryotic genomes

“Phylogenetic profiling” is based on the hypothesis that during evolution functionally or physically interacting genes are likely to be inherited or eliminated in a codependent manner. Creating presence–absence profiles of orthologous genes is now a common and powerful way of identifying functionally associated genes. In this approach, correctly determining orthology, as a means of identifying functional equivalence between two genes, is a critical and nontrivial step and largely explains why previous work in this area has mainly focused on using presence–absence profiles in prokaryotic species. Here, we demonstrate that eukaryotic genomes have a high proportion of multigene families whose phylogenetic profile distributions are poor in presence–absence information content. This feature makes them prone to orthology mis-assignment and unsuited to standard profile-based prediction methods. Using CATH structural domain assignments from the Gene3D database for 13 complete eukaryotic genomes, we have developed a novel modification of the phylogenetic profiling method that uses genome copy number of each domain superfamily to predict functional relationships. In our approach, superfamilies are subclustered at ten levels of sequence identity—from 30% to 100%—and phylogenetic profiles built at each level. All the profiles are compared using normalised Euclidean distances to identify those with correlated changes in their domain copy number. We demonstrate that two protein families will “auto-tune” with strong co-evolutionary signals when their profiles are compared at the similarity levels that capture their functional relationship. Our method finds functional relationships that are not detectable by the conventional presence–absence profile comparisons, and it does not require a priori any fixed criteria to define orthologous genes.     

The Extratropical Northern Hemisphere Temperature Reconstruction during the Last Millennium Based on a Novel Method

Large-scale climate history of the past millennium reconstructed solely from tree-ring data is prone to underestimate the amplitude of low-frequency variability. In this paper, we aimed at solving this problem by utilizing a novel method termed “MDVM”, which was a combination of the ensemble empirical mode decomposition (EEMD) and variance matching techniques. We compiled a set of 211 tree-ring records from the extratropical Northern Hemisphere (30–90°N) in an effort to develop a new reconstruction of the annual mean temperature by the MDVM method. Among these dataset, a number of 126 records were screened out to reconstruct temperature variability longer than decadal scale for the period 850–2000 AD. The MDVM reconstruction depicted significant low-frequency variability in the past millennium with evident Medieval Warm Period (MWP) over the interval 950–1150 AD and pronounced Little Ice Age (LIA) cumulating in 1450–1850 AD. In the context of 1150-year reconstruction, the accelerating warming in 20^th century was likely unprecedented, and the coldest decades appeared in the 1640s, 1600s and 1580s, whereas the warmest decades occurred in the 1990s, 1940s and 1930s. Additionally, the MDVM reconstruction covaried broadly with changes in natural radiative forcing, and especially showed distinct footprints of multiple volcanic eruptions in the last millennium. Comparisons of our results with previous reconstructions and model simulations showed the efficiency of the MDVM method on capturing low-frequency variability, particularly much colder signals of the LIA relative to the reference period. Our results demonstrated that the MDVM method has advantages in studying large-scale and low-frequency climate signals using pure tree-ring data.