Stepwise Pattern Research Articles

Language difficulties are a shared risk factor for both reading disorder and mathematics disorder

Disorders of reading and mathematics co-occur at greater than chance rates, but they are often studied separately. This article reports the reading and arithmetic outcomes at 9 years of age from a longitudinal study of 224 children at high risk for dyslexia. Using a cutoff at the 10th centile, groups of children with reading disorder (RD), mathematics disorder (MD), and comorbid reading disorder and math disorder (RD&MD) were identified. The risk of these disorders was elevated in children selected in preschool with language difficulties or at family risk for dyslexia. There was a high degree of comorbidity between RD and MD, and many cases—particularly in the comorbid group—also reached the diagnostic threshold for developmental language disorder (DLD). On measures of language, phoneme awareness, rapid automatized naming (RAN) digits, and rated inattention, there was a stepwise pattern: RD > MD > RD&MD. Poor language was associated with each disorder and appears to be a cognitive risk factor for RD, MD, and RD&MD. These findings suggest that there are shared genetic risk factors operating for both RD and MD.

Atypical Brain Asymmetry in Autism—A Candidate for Clinically Meaningful Stratification

BackgroundAutism spectrum disorder (“autism”) is a highly heterogeneous neurodevelopmental condition with few effective treatments for core and associated features. To make progress we need to both identify and validate neural markers that help to parse heterogeneity to tailor therapies to specific neurobiological profiles. Atypical hemispheric lateralization is a stable feature across studies in autism, but its potential as a neural stratification marker has not been widely examined. MethodsIn order to dissect heterogeneity in lateralization in autism, we used the large EU-AIMS (European Autism Interventions—A Multicentre Study for Developing New Medications) Longitudinal European Autism Project dataset comprising 352 individuals with autism and 233 neurotypical control subjects as well as a replication dataset from ABIDE (Autism Brain Imaging Data Exchange) (513 individuals with autism, 691 neurotypical subjects) using a promising approach that moves beyond mean group comparisons. We derived gray matter voxelwise laterality values for each subject and modeled individual deviations from the normative pattern of brain laterality across age using normative modeling. ResultsIndividuals with autism had highly individualized patterns of both extreme right- and leftward deviations, particularly in language, motor, and visuospatial regions, associated with symptom severity. Language delay explained most variance in extreme rightward patterns, whereas core autism symptom severity explained most variance in extreme leftward patterns. Follow-up analyses showed that a stepwise pattern emerged, with individuals with autism with language delay showing more pronounced rightward deviations than individuals with autism without language delay. ConclusionsOur analyses corroborate the need for novel (dimensional) approaches to delineate the heterogeneous neuroanatomy in autism and indicate that atypical lateralization may constitute a neurophenotype for clinically meaningful stratification in autism.

Relationship Between Body Mass Index and Extrapyramidal Symptoms in Asian Patients with Schizophrenia: The Research on Asian Psychotropic Prescription Patterns for Antipsychotics (REAP-AP).

Although an inverse relationship between body mass index (BMI) and Parkinson disease (PD) has been repeatedly reported, to our knowledge, the relationship between BMI and antipsychotic-induced extrapyramidal symptoms (EPS) has rarely been studied in patients with schizophrenia. Our study aimed to evaluate the relationship between BMI and EPS in patients with schizophrenia. Using data from the Research on Asian Psychotropic Prescription Patterns for Antipsychotics (REAP-AP) study, we compared the prevalence of EPS in 1448 schizophrenia patients stratified as underweight, normal range, overweight pre-obese, overweight obese I, overweight obese II, and overweight obese III according to the World Health Organization (WHO) classification system for body weight status, and with underweight, normal range, overweight at risk, overweight obese I, and overweight obese II according to the Asia-Pacific obesity classification. In the first step of the WHO classification system for body weight status, adjusting for the potential effects of confounding factors, the multinomial logistic regression model revealed that underweight was significantly associated with greater rates of bradykinesia and muscle rigidity, and a lower rate of gait disturbance. In the second step of the Asia-Pacific obesity classification, adjusting for the potential effects of confounding factors, the multinomial logistic regression model revealed that underweight was significantly associated with a higher rate of muscle rigidity. Findings of the present study consistently revealed that underweight was associated with a greater rate of muscle rigidity in a stepwise pattern among Asian patients with schizophrenia. Although the mechanism underlying the inverse relationship between BMI and muscle rigidity cannot be sufficiently explained, it is speculated that low BMI may contribute to the development of muscle rigidity regardless of antipsychotic "typicality" and dose in patients with schizophrenia.

Two-step extinction of Late Cretaceous marine vertebrates in northern Gulf of Mexico prolonged biodiversity loss prior to the Chicxulub impact

Recent studies on mass extinctions are often based on the global fossil record, but data from selected paleogeographic regions under a relatively constant paleoenvironmental setting can also provide important information. Eighty-nine marine vertebrate species, including cartilaginous and bony fish and marine reptiles, from northern Gulf of Mexico – located about 500 km from the Chicxulub crater – offer a unique opportunity to determine an extinction process during the last 20 million years of the Late Cretaceous. Our diversity data show two separate extinction events: (i) the ‘Middle Campanian Crisis’ (about 77 Mya) and (ii) the end-Maastrichtian (66 Mya) events. Whether this stepwise pattern of extinctions occurred locally or globally cannot be determined at present due to the lack of a dataset of the marine vertebrate record for reliable comparison. However, this stepwise pattern including the Middle Campanian and end-Maastrichtian events for, at least, a 13 million-year interval indicates long-term global marine environmental changes (e.g., regression, ocean water chemistry change). Because most Cretaceous marine vertebrates already disappeared in the Gulf of Mexico prior to the latest Maastrichtian, the Chicxulub Impact may not be considered as the most devastating extinction event for the community.

Improving prediction of two ENSO types using a multi-model ensemble based on stepwise pattern projection model

This study focuses on improving prediction of the two types of ENSO by combining multi-model ensemble (MME) with a statistical error correction method that is based on a stepwise pattern projection and applied to all models before doing the MME. We evaluate such a combinational approach using five dynamical model datasets from the North American Multi-model Ensemble (NMME) project for the period of 1982–2010. The prediction skills of the proposed MME show an improvement over most tropical Pacific regions. With regard to the two ENSO types, improvements in prediction skills of the proposed MME are particularly evident for the Niño indices for short lead time. The differences between the Eastern Pacific and Central Pacific ENSO types are more pronounced in the corrected forecasts compared with the uncorrected ones. The zonal center position of sea surface temperature anomalies for the corrected MME is closer to the observed than that for the uncorrected MME. The results indicate that reducing prediction errors of each model member by a good correction method before applying the MME method can provide an effective way for empirically improving forecasts of the two ENSO types.

EFFECT OF STEP PATTERN TECHNIQUE TO SIDE AND MOVEMENT STEP STRAIGHT AHEAD TO SABIT KICKNESS

This study aims to determine the effect of exercise on stepwise pattern and exercise a straight forward move towards crescent kick agility in UKM PSHT students of Muhammadiyah University of East Kalimantan (UMKT). The population in this study were students who were still actively participating in the UKM PSHT UMKT. Sampling uses a random sampling system, divided into 2 groups, namely group A by practicing stepwise patterns and group B by practicing a straight forward step. Each group consists of 10 sample people, so the total sample is 20 people. The results showed that: (1) There was the effect of training the step-by-step pattern on crescent kick agility on UMKT PSHT UKM students who obtained the value of tcount = 9.531> t table = 2.262 with a probability value of 0.000 <α 0.05. (2) There is the effect of a straight-forward exercise on crescent kick agility on UMKT PSHT UKM students who obtained a tcount = 6.975> t table = 2.262 with a significance probability value of 0.000 <α 0.05. (3) There is a difference in the effect of step-to-side pattern training and straight-forward motion training on crescent kick agility in Mulawarman University PSHT UKM students by obtaining a tcount = 4.348> t table = 1.734 with a significance probability value of 0.000 <α 0.05.

Creep properties of clastic soil in a reactivated slow-moving landslide in the Three Gorges Reservoir Region, China

Most slow-moving landslides in the Three Gorges Reservoir (TGR) region of China are characterized by pre-existing shear surfaces. The large deformation within the shear zones usually gives rise to clastic soil formation. The creep properties have large influence on the kinematic feature of landslides. In this paper, we report an in-situ direct shear creep test carried out in the shear zone of a reactivated slow-moving landslide in the TGR region. Correspondingly, some laboratory ring shear creep tests are carried out to interpret the movement pattern of this landslide. The shear zone soil exhibits similar non-attenuating creep responses in both the in-situ direct shear and laboratory ring shear creep tests. At the same stress level, however, the in-situ direct shear creep test yields a larger rate of creep displacement due to shearing along the landslide direction. In the ring shear creep tests, at the prepeak stage, the critical creep stress that triggers creep failure is slightly lower than the peak shear strength but much larger than the residual strength; at the postfailure stage, the critical creep stress of the shear-zone soil is equal to the residual shear strength. The rate-dependent residual shear strength may account for the stepwise movement pattern of the landslide.

C[sbnd]C motif chemokine ligand 16 inhibits the progression of liver cirrhosis via inactivating hepatic stellate cells

BackgroundLiver cirrhosis results from many forms of chronic damage, characterized by accumulation of extracellular matrix. The present study aimed to explore a potential non-invasive biomarker and its mechanism in the progression of liver cirrhosis. MethodsGene Expression Omnibus (GEO) dataset (GSE15654, n = 216) was analyzed to screen genes associated with progression of liver cirrhosis. A total of 181 plasma samples, including healthy control (HC, n = 20), chronic hepatitis B (CHB, n = 77) and HBV-related liver cirrhosis (LC, n = 84), were enrolled for validation. In vitro and in vivo experiments were employed for the mechanistic investigation. ResultsGEO dataset analysis showed that relatively low mRNA-expression of CC motif chemokine ligand 16 (CCL16) was associated with elevated Child-Pugh score (P = 0.034) and worse prognosis (P = 0.025). Plasma CCL16 level decreased in a stepwise pattern, with a median concentration of 10.29, 6.57 and 4.47 ng/mL in the HC, CHB and LC groups, respectively (P<0.001). Low plasma CCL16 was significantly related to hepatic dysfunction both in the CHB and LC groups (P<0.05). Combination of CCL16 and ALT showed improved distinguishing capability for LC compared to either alone. In vitro, CCL16 expression was downregulated by lipopolysaccharide and hypoxia. Overexpression of CCL16 from human normal liver cell line (LO2) reduced the extracellular matrix associated proteins (Col1 and Col4) in human hepatic stellate cell line (LX-2). In vivo, the pathological feature of cirrhosis was alleviated by the hepatocyte-specific expression of CCL16. ConclusionsCCL16 could be a feasible plasma marker to predict the occurrence and progression of liver cirrhosis. CCL16 might impact liver cirrhosis through inactivating hepatic stellate cells.

Land Use Change and Its Impact of Ecosystem Service Value in Yarlung Zangbo River Basin in Southern of Qinghai-Tibet Plateau

Scientific determination of ecosystem service values (ESVs) is the basis and premise of realizing sustainable management of the regional ecosystem. Therefore, it is of great significance to explore the dynamic evolution of ESV in Qinghai-Tibet Plateau (QTP) to maintain the plateau landscape diversity and ecological environment protection. This paper constructed a compre-hensive basin analysis perspective of horizontal distribution, vertical distribution, and basin gradient to analyze the dynamic evolution of ESV in the Yarlung Zangbo River Basin (YZRB). The results showed that: The total ESVs of YZRB increased from 1980 to 2015, in which the ESVs of grassland and water decreased, and ESVs of other sites increased. The changes in ESVs in different land-use types had obvious differences in basin gradients. In general, ESVs presented a stepwise distribution pattern of “upper

Different Risk Target Volumes for Nasopharyngeal Carcinoma Treated with Simultaneous Integrated Boost Intensity-Modulated Radiotherapy

Background and Objectives: Although intensity-modulated radiotherapy (IMRT) provides promising survival advantages and fewer late complications in patients with nasopharyngeal cancer (NPC), appropriated target volumes and prescribed doses are still being explored. This study aimed to propose different risk target volumes and corresponding prescribed doses in our center and to evaluate the physical basis and efficacy of this protocol based on the long-term survival of NPC patients.Methods and Materials: We retrospectively assessed patients with histology-proven non-metastatic NPC treated with definitive IMRT using our protocol of different risk target volumes and corresponding prescribed doses based on the orderly stepwise pattern of tumor spread. We described the delineation for different risk target volumes and the design of IMRT planning for an NPC case. Additionally, we compared the dosimetric distributions between the China protocol and our protocol through two NPC cases. The patterns of failure and locoregional control were the primary endpoints. All survival outcomes were calculated using the Kaplan-Meier method.Results: From January 2013 to December 2014, a total of 335 patients were treated; the median follow-up for patients who survived was 70 months. All patients completed IMRT using our protocol. Twenty-five patients developed locoregional recurrence, and all recurrences occurred within the high-dose target volumes. The rates of locoregional recurrence-free survival, distant metastasis-free survival, progression-free survival, and overall survival at 5 years were 92.2%, 92.1%, 85.9%, and 86.3%, respectively. The biological effective doses of the prescribed doses in our protocol were similar to those of the China and 0615 protocols. Moreover, our protocol offered a reduction in D1 and D2 in the primary gross tumor volume (GTV), while V30 and V40 in normal tissues were lower.Conclusion: Our protocol of different risk target volume delineations and corresponding prescribed doses based on the stepwise pattern of tumor spread resulted in favorable locoregional control with no relapse outside the GTV.

Mining treatment patterns of glucose-lowering medications for type 2 diabetes in the Netherlands

Rationale and objectivesDifferent classes of glucose-lowering medications are used for patients with type 2 diabetes mellitus (T2DM) management. It is unclear how often these medications are prescribed in clinical practice....

Nigrosome 1 imaging in REM sleep behavior disorder and its association with dopaminergic decline.

ObjectivesRapid eye movement sleep behavior disorder (RBD) patients have a high risk of developing a Parkinsonian disorder, offering an opportunity for neuroprotective intervention. Predicting near‐term conversion, however, remains a challenge. Dopamine transporter imaging, while informative, is expensive and not widely available. Here, we investigate the utility of susceptibility‐weighted MRI (SWI) to detect abnormalities of the substantia nigra in RBD, and explore their association with striatal dopaminergic deficits.MethodsSWI of the substantia nigra was performed in 46 RBD patients, 27 Parkinson’s patients, and 32 control subjects. Dorsal nigral hyperintensity (DNH) was scored by two blinded raters, and separately quantified using a semiautomated process. Forty‐two RBD patients were also imaged with 123I‐ioflupane single‐photon emission computed tomography (DaT SPECT/CT).ResultsConsensus visual DNH classification was possible in 87% of participants. 27.5% of RBD patients had lost DNH, compared with 7.7% of control subjects and 96% of Parkinson’s patients. RBD patients lacking DNH had significantly lower putamen dopaminergic SPECT/CT activity compared to RBD patients with DNH present (specific uptake ratios 1.89 vs. 2.33, P = 0.002). The mean quantified DNH signal intensity declined in a stepwise pattern, with RBD patients having lower intensity than controls (0.837 vs. 0.877, P = 0.01) but higher than PD patients (0.837 vs. 0.765, P < 0.001).InterpretationOver one quarter of RBD patients have abnormal substantia nigra SWI reminiscent of Parkinson’s, which is associated with a greater dopaminergic deficit. This modality may help enrich neuroprotective trials with early converters.

Assessment of the Sea Surface Temperature Predictability Based on Multimodel Hindcasts

Abstract Based on historical forecasts of four individual forecasting systems, we conducted multimodel ensembles (MME) to predict the sea surface temperature anomaly (SSTA) variability and assessed these methods from a deterministic and probabilistic point of view. To investigate the advantages and drawbacks of different deterministic MME methods, we used simple averaged MME with equal weighs (SCM) and the stepwise pattern projection method (SPPM). We measured the probabilistic forecast accuracy by Brier skill score (BSS) combined with its two components: reliability (Brel) and resolution (Bres). The results indicated that SCM showed a high predictability in the tropical Pacific Ocean, with a correlation exceeding 0.8 with a 6-month lead time. In general, the SCM outperformed the SPPM in the tropics, while the SPPM tend to show some positive effect on the correction when at long lead times. Corrections occurred for the spring predictability barrier of ENSO, in particular for improvements when the correlation was low or the RMSE was large using the SCM method. These qualitative results are not susceptible to the selection of the hindcast periods, it is as a rule rather by chance of these individual systems. Performance of our probabilistic MME was better than the Climate Forecast System version2 (CFSv2) forecasts in forecasting COLD, NEUTRAL, and WARM SSTA categories for most regions, mainly due to the contribution of Brel, indicating more adequate ensemble construction strategies of the MME system superior to the CFSv2.

Differential expression of miRNAs regulating NF-κB and STAT3 crosstalk during colitis-associated tumorigenesis

Inflammatory bowel disease (IBD) is mostly responsible for the development of colitis-associated colon cancer. Of the several signaling pathways involved in colonic inflammation, the activation and crosstalk between NF-κB and STAT3 serve as the pivotal regulatory hubs that regulate epithelial tumorigenesis by linking inflammation with cancer development. Understanding the molecular mechanisms regulating the crosstalk between NF-κB and STAT3 will help in targeting these signaling pathways and halt epithelial tumorigenesis. MicroRNAs (miRNAs) play important role in the regulation of NF-κB and STAT3 and function in a positive- or negative feedback loop to regulate the crosstalk of these transcription factor.In the present study we evaluated the aberrant expression of a selected panel of miRNAs (miR-181b, miR-31, miR-34a, miR-146b, miR-221, and miR-155) that regulate the crosstalk between NF-κB and STAT3 during colitis-associated tumorigenesis. We used the stepwise colorectal carcinogenesis murine model known as Azoxymethane (AOM)/Dextran sodium sulphate (DSS) to recapitulate the different stages of tumorigenesis. Our results revealed that the expression of the selected miRNAs changed dynamically in a stepwise pattern as colonic tissue transforms from normal to actively inflamed to neoplastic state, in accordance with the gradual activation of NF-κB and STAT3, suggesting that the aberrant expression of these miRNAs could function as the epigenetic switch between inflammation and colorectal tumorigenesis. We were able to elucidate the contribution of miRNAs in the NF-κB - STAT3 crosstalk during the stepwise development of colitis-associated carcinoma, and this could improve our understanding of the molecular pathology of colorectal tumorigenesis and even suggesting a therapeutic strategy by modulating the expression of these regulating miRNAs.

Warming temperatures are impacting the hydrometeorological regime of Russian rivers in the zone of continuous permafrost

Abstract. Large Arctic river basins experience substantial variability in climatic, landscape, and permafrost conditions. However, the processes behind the observed changes at the scale of these basins are relatively poorly understood. While most studies have been focused on the “Big 6” Arctic rivers – the Ob', Yenisey, Lena, Mackenzie, Yukon, and Kolyma – few or no assessments exist for small and medium-sized river basins, such as the Yana and Indigirka River basins. Here, we provide a detailed analysis of streamflow data from 22 hydrological gauges in the Yana and Indigirka River basins with a period of observation ranging from 35 to 79 years up to 2015. These river basins are fully located in the zone of continuous permafrost. Our analysis reveals statistically significant (p&lt;0.05) positive trends in the monthly streamflow time series during the autumn–winter period for most of the gauges. The streamflow increases in a stepwise pattern (post-1981) for 17 out of 22 gauges in September (average trend value for the period of record is 58 % or 9.8 mm) and 15 out of 22 gauges in October (61 % or 2.0 mm). The positive trends are seen in 9 out of 19 rivers that do not freeze in November (54 %, 0.4 mm) and 6 out of 17 rivers that do not freeze in December (95 %, 0.15 mm). Precipitation is shown to decrease in late winter by up to 15 mm over the observational period. Additionally, about 10 mm of precipitation that used to fall as snow at the beginning of winter now falls as rain. Despite the decrease in winter precipitation, no decrease in streamflow has been observed during the spring freshet in May and June in the last 50 years (from 1966); moreover, five gauges show an increase of 86 % or 12.2 mm in spring floods via an abrupt change in 1987–1993. The changes in spring freshet start date are identified for 10 gauges; the earlier onset in May varies from 4 to 10 d over the observational period. We conclude that warmer temperatures due to climate change are impacting the hydrological regime of these rivers via changes in precipitation type (rain replacing snow). Other factors, such as the melting of permafrost, glaciers, and aufeis or changes in groundwater conditions, are likely to contribute as well; however, no direct observations of these changes are available. The changes in streamflow can have a significant impact on the ecology of the zone of continuous permafrost, while the increasing freshwater fluxes to the Arctic Ocean can impact the Arctic thermohaline circulation.

White Matter Abnormalities in Major Depression Biotypes Identified by Diffusion Tensor Imaging.

Identifying data-driven biotypes of major depressive disorder (MDD) has promise for the clarification of diagnostic heterogeneity. However, few studies have focused on white-matter abnormalities for MDD subtyping. This study included 116 patients with MDD and 118 demographically-matched healthy controls assessed by diffusion tensor imaging and neurocognitive evaluation. Hierarchical clustering was applied to the major fiber tracts, in conjunction with tract-based spatial statistics, to reveal white-matter alterations associated with MDD. Clinical and neurocognitive differences were compared between identified subgroups and healthy controls. With fractional anisotropy extracted from 20 fiber tracts, cluster analysis revealed 3 subgroups based on the patterns of abnormalities. Patients in each subgroup versus healthy controls showed a stepwise pattern of white-matter alterations as follows: subgroup 1 (25.9% of patient sample), widespread white-matter disruption; subgroup 2 (43.1% of patient sample), intermediate and more localized abnormalities in aspects of the corpus callosum and left cingulate; and subgroup 3 (31.0% of patient sample), possible mild alterations, but no statistically significant tract disruption after controlling for family-wise error. The neurocognitive impairment in each subgroup accompanied the white-matter alterations: subgroup 1, deficits in sustained attention and delayed memory; subgroup 2, dysfunction in delayed memory; and subgroup 3, no significant deficits. Three subtypes of white-matter abnormality exist in individuals with major depression, those having widespread abnormalities suffering more neurocognitive impairments, which may provide evidence for parsing the heterogeneity of the disorder and help optimize type-specific treatment approaches.

A machine learning based study on pedestrian movement dynamics under emergency evacuation

Knowledge of evacuees' movement dynamics is crucial to building safety design and evacuation management. Although it is recognized that stepwise movement is the fundamental element to construct the whole evacuation process, movement pattern and its influencing factors are still not well understood. In this study, we explored the potential of adopting machine learning methods to study evacuees' stepwise movement1 dynamics based on two videos of quasi-emergency evacuation experiments. The movement patterns were categorized through Two-step Cluster Analysis and principal influencing factors were identified through Principal Component Analysis. The relationship between the movement patterns and the principal components were investigated using different modeling methods: traditional method (Multinomial Logit Model, MLM) and machine learning methods (Decision Tree, Support Vector Machine, K-Nearest Neighbor, and Artificial Neural Network). Results from two experimental videos showed reasonable consistency and the main findings are: (1) Distance to the target exit has the most pronounced effect on a single evacuee's stepwise movement pattern. (2) Surrounding evacuees' actions also have significant and complex influence on a single evacuee's stepwise movement pattern. (3) MLM showed comparable prediction accuracy with machine learning methods when the scenario is simple. The superiority of machine learning became apparent when the scenario was more complex, with a maximum enhancement of 13.25% in prediction accuracy. Each machine learning method demonstrated distinct features and advantages in different aspects.

Common and specific altered amplitude of low-frequency fluctuations in Parkinson's disease patients with and without freezing of gait in different frequency bands.

Freezing of gait (FOG), a disabling symptom of Parkinson's disease (PD), severely affects PD patients' life quality. Previous studies found neuropathologies in functional connectivity related to FOG, but few studies detected abnormal regional activities related to FOG in PD patients. In the present study, we analyzed the amplitude of low-frequency fluctuations (ALFF) to detect brain regions showing abnormal activity in PD patients with FOG (PD-with-FOG) and without FOG (PD-without-FOG). As different frequencies of neural oscillations in brain may reflect distinct brain functional and physiological properties, we conducted this study in three frequency bands, slow-5 (0.01-0.027Hz), slow-4 (0.027-0.073Hz), and classical frequency band (0.01-0.08Hz). We acquired rs-fMRI data from 18 PD-with-FOG patients, 18 PD-without-FOG patients, and 17 healthy controls, then calculated voxel-wise ALFF across the whole brain and compared ALFF among the three groups in each frequency band. We found: (1) in slow-5, both PD-with-FOG and PD-without-FOG patients showed lower ALFF in the bilateral putamen compared to healthy controls, (2) in slow-4, PD-with-FOG patients showed higher ALFF in left inferior temporal gyrus (ITG) and lower ALFF in right middle frontal gyrus (MFG) compared to either PD-without-FOG patients or healthy controls, (3) in classical frequency band, PD-with-FOG patients also showed higher ALFF in ITG compared to either PD-without-FOG patients or healthy controls. Furthermore, we found that ALFF in MFG and ITG in slow-4 provided the highest classification accuracy (96.7%) in distinguishing PD-with-FOG from PD-without-FOG patients by using a stepwise multivariate pattern analysis. Our findings indicated frequency-specific regional spontaneous neural activity related to FOG, which may help to elucidate the pathogenesis of FOG.

Multistage dynamics of Hg2+-DNA interactions: a single-molecule study.

The metal ion-DNA interaction is key to biochemical processes and has applications in areas such as metal ion sensors and DNA nanomachines. For example, the formation of the T-Hg2+-T structure has been used in technologies such as DNA-based mercuric ion sensors. Though the interaction is widely used for practical purposes, the underlying mechanism has not been fully understood. In the present study, we used magnetic tweezers to explore the interactions between λ-DNA and two metal ions, Hg2+ and Cd2+, at the single-molecule level. Both metal ions caused considerable DNA conformational changes. The resulting DNA compaction dynamics were related to the ion concentration and the exerted force. The increase in the ion concentration promoted DNA compaction, whereas exerting greater forces inhibited this process. Application of a high force generated two-stage dynamics of the Hg2+-DNA interaction. However, at a sufficiently high Hg2+ concentration, a lower force led to a three-stage process. In contrast, the curves of the binding of Cd2+ ions to DNA had a stepwise pattern. Both the AFM scanning results and the single-molecule measurements confirmed that Hg2+ influences the DNA conformation in a more pronounced manner than Cd2+. The multistage Hg2+-DNA interaction was considered to be a result of the different binding mechanisms, including the mismatched base-pair formation. A model was then proposed to explain the peculiar dynamics.

The Genome Landscape of Tibetan Sheep Reveals Adaptive Introgression from Argali and the History of Early Human Settlements on the Qinghai-Tibetan Plateau.

Tibetan sheep are the most common and widespread domesticated animals on the Qinghai–Tibetan Plateau (QTP) and have played an essential role in the permanent human occupation of this high-altitude region. However, the precise timing, route, and process of sheep pastoralism in the QTP region remain poorly established, and little is known about the underlying genomic changes that occurred during the process. Here, we investigate the genomic variation in Tibetan sheep using whole-genome sequences, single nucleotide polymorphism arrays, mitochondrial DNA, and Y-chromosomal variants in 986 samples throughout their distribution range. We detect strong signatures of selection in genes involved in the hypoxia and ultraviolet signaling pathways (e.g., HIF-1 pathway and HBB and MITF genes) and in genes associated with morphological traits such as horn size and shape (e.g., RXFP2). We identify clear signals of argali (Ovis ammon) introgression into sympatric Tibetan sheep, covering 5.23–5.79% of their genomes. The introgressed genomic regions are enriched in genes related to oxygen transportation system, sensory perception, and morphological phenotypes, in particular the genes HBB and RXFP2 with strong signs of adaptive introgression. The spatial distribution of genomic diversity and demographic reconstruction of the history of Tibetan sheep show a stepwise pattern of colonization with their initial spread onto the QTP from its northeastern part ∼3,100 years ago, followed by further southwest expansion to the central QTP ∼1,300 years ago. Together with archeological evidence, the date and route reveal the history of human expansions on the QTP by the Tang–Bo Ancient Road during the late Holocene. Our findings contribute to a depth understanding of early pastoralism and the local adaptation of Tibetan sheep as well as the late-Holocene human occupation of the QTP.