Spatiotemporal multi-omics: exploring molecular landscapes in aging and regenerative medicine.

Aging and regeneration represent complex biological phenomena that have long captivated the scientific community. To fully comprehend these processes, it is essential to investigate molecular dynamics through a lens that encompasses both spatial and temporal dimensions. Conventional omics methodologies, such as genomics and transcriptomics, have been instrumental in identifying critical molecular facets of aging and regeneration. However, these methods are somewhat limited, constrained by their spatial resolution and their lack of capacity to dynamically represent tissue alterations. The advent of emerging spatiotemporal multi-omics approaches, encompassing transcriptomics, proteomics, metabolomics, and epigenomics, furnishes comprehensive insights into these intricate molecular dynamics. These sophisticated techniques facilitate accurate delineation of molecular patterns across an array of cells, tissues, and organs, thereby offering an in-depth understanding of the fundamental mechanisms at play. This review meticulously examines the significance of spatiotemporal multi-omics in the realms of aging and regeneration research. It underscores how these methodologies augment our comprehension of molecular dynamics, cellular interactions, and signaling pathways. Initially, the review delineates the foundational principles underpinning these methods, followed by an evaluation of their recent applications within the field. The review ultimately concludes by addressing the prevailing challenges and projecting future advancements in the field. Indubitably, spatiotemporal multi-omics are instrumental in deciphering the complexities inherent in aging and regeneration, thus charting a course toward potential therapeutic innovations.

Predictive Value of Nutritional Risk for All-Cause Death and Functional Outcomes in Chinese Elderly Patients with Acute Stroke: A 3-Year Follow-Up Study.

Purpose: To explore the predictive value of nutritional risk for all-cause death and functional outcomes among elderly acute stroke patients. Patients and Methods: A total of 479 elderly acute stroke patients were enrolled in this study. The nutritional risk of patients was screened by the GNRI and NRS-2002. The primary outcome was all-cause death, and the secondary outcome was poor prognosis defined as a modified Rankin Scale (mRS) score ≥3. Results: Based on the NRS-2002, patients with nutritional risk had a higher risk of all-cause death at 3 months (adjusted OR: 3.642, 95% CI 1.046~12.689) and at 3 years (adjusted OR: 2.266, 95% CI 1.259~4.076) and a higher risk of adverse functional outcomes at 3 months (adjusted OR: 2.748, 95% CI 1.518~4.972. Based on the GNRI, compared to those without nutritional risk, patients with mild malnutrition also had a higher risk of all-cause death at 3 months (adjusted OR: 7.186, 95% CI 1.550~33.315) and at 3 years (adjusted OR: 2.255, 95% CI 1.211~4.199) and a higher risk of adverse functional outcomes at 3 months (adjusted OR: 1.947, 95% CI 1.030~3.680), so patients with moderate and severe malnutrition had a higher risk of all-cause death at 3 months (adjusted OR: 6.535, 95% CI 1.380~30.945) and at 3 years (adjusted OR: 2.498, 95% CI 1.301~4.799) and a higher risk of adverse functional outcomes at 3 months (adjusted OR: 2.213, 95% CI 1.144~4.279). Conclusion: Nutritional risk increases the risk of poor short-term and long-term outcomes in elderly patients with acute stroke. For elderly stroke patients, we should pay attention to early nutritional risk screening, and effective intervention should be provided to improve the prognosis of such patients.

A portable, integrated microfluidics for rapid and sensitive diagnosis of Streptococcus agalactiae in resource-limited environments.

Streptococcus agalactiae (Group B Streptococcus, GBS) has been the leading cause of infections in newborns. Rapid and accurate diagnosis of GBS in pregnant women is a deterministic strategy to prevent newborn infection. Conventional detection methods based on nucleic acid amplification assay have been applied in GBS diagnosis in central laboratories, with demonstrated high sensitivity. However, their heavy dependence on instrumentation and trained technicians forms remarkable obstacles to GBS detection in wide scenarios, including self-testing, and bedside-/community-screening. Furthermore, the structures of GBS bring about extra challenges to the nucleic acid extraction and purification. Novel GBS diagnosis platforms integrating sample processing, amplification, and read-out, are highly desired in clinical. Here, we report a portable, integrated microfluidics that enables rapid extraction of DNA from sampling swabs (<10 min), power-free DNA amplification (<30 min), and simple read-out in GBS detection. The platform works without an external pump, achieving rapid and highly efficient DNA extraction from clinical samples, with a significantly reduced time from 6 h to less than 50 min. Systematic clinical tests based on 47 patient samples validated the high performance of the platform, highlighted with a low limit of detection (LOD, 103 copies/ml), high sensitivity (100%), and specificity (100%). Head-to-head comparisons showed that the device improved the LOD by an order of magnitude than the traditional PCR method, showing a simple yet powerful POCT platform for home-/community-based testing towards GBS (and other pathogens) prevention in remote areas.

Heterologous expression and characterization of an M4 family extracellular metalloprotease for detergent application.

Proteolytic enzymes stand out as the most widely employed category utilized in manufacturing industry. A new protease was separated from Planococcus sp.11815 strain and named as nprS-15615 in this research. The gene of this protease has not been reported, and its enzymatic properties have been studied for the first time. To enhance enzyme production, the Planococcus sp. protease gene was expressed in Bacillus licheniformis 2709. The expression level of nprS-15615 was observed under the control of regulatory elements PaprE. nprS-15615 protease activity reached 1186.24±32.87 U/mL after 48 hours of cultivation in shake flasks which was nearly four times the output of the original bacteria (291.38±25.73U/mL). The optimum temperature and pH of the recombinant protease were 30 ℃ and 8.0, respectively.The enzyme exhibited the highest capacity for hydrolyzing casein and demonstrated resilience towards a NaCl concentration of 10.0% (wt/v). Furthermore, in the presence of 0.5% surfactants, the recombinant protease activity can maintain above 75%, and with the existence of 0.5% liquid detergents, there was basically no loss of enzyme activity which indicated that nprS-15615 had good compatibility with surfactants and liquid detergents. In addition, npS-15615 performed well in the washing experiment, and the washing effect at 20 ℃ can be significantly improved by adding crude enzyme solution in the washing process.

A model for predicting physical function upon discharge of hospitalized older adults in Taiwan-a machine learning approach based on both electronic health records and comprehensive geriatric assessment.

Background: Predicting physical function upon discharge among hospitalized older adults is important. This study has aimed to develop a prediction model of physical function upon discharge through use of a machine learning algorithm using electronic health records (EHRs) and comprehensive geriatrics assessments (CGAs) among hospitalized older adults in Taiwan. Methods: Data was retrieved from the clinical database of a tertiary medical center in central Taiwan. Older adults admitted to the acute geriatric unit during the period from January 2012 to December 2018 were included for analysis, while those with missing data were excluded. From data of the EHRs and CGAs, a total of 52 clinical features were input for model building. We used 3 different machine learning algorithms, XGBoost, random forest and logistic regression. Results: In total, 1,755 older adults were included in final analysis, with a mean age of 80.68 years. For linear models on physical function upon discharge, the accuracy of prediction was 87% for XGBoost, 85% for random forest, and 32% for logistic regression. For classification models on physical function upon discharge, the accuracy for random forest, logistic regression and XGBoost were 94, 92 and 92%, respectively. The auROC reached 98% for XGBoost and random forest, while logistic regression had an auROC of 97%. The top 3 features of importance were activity of daily living (ADL) at baseline, ADL during admission, and mini nutritional status (MNA) during admission. Conclusion: The results showed that physical function upon discharge among hospitalized older adults can be predicted accurately during admission through use of a machine learning model with data taken from EHRs and CGAs.

Apelin-36 alleviates LPS-induced trophoblast cell injury by inhibiting GRP78/ASK1/JNK signaling.

Pre-eclampsia (PE) is a type of hypertensive disorder of pregnancy that poses a serious threat to the health of both mother and fetus. Inhibition of the inflammatory environment on trophoblast cells is of great significance to improve PE. Apelin-36 is an endogenous active peptide with strong anti-inflammatory activity. Therefore, this study aims to investigate the effects of Apelin-36 on lipopolysaccharide (LPS)-induced trophoblast cells and its potential mechanism. The levels of inflammatory factors (TNF-α, IL-8, IL-6 and MCP-1) were detected by reverse transcription-quantitative PCR (RT-qPCR). The proliferation, apoptosis, migration and invasion capacities in trophoblast cells were detected by CCK-8, TUNEL staining, wound healing and Transwell assays, respectively. GRP78 was overexpressed by cell transfection. Western blot was applied for the identification of protein levels. Apelin concentration-dependently decreased the expression of inflammatory cytokines and p-p65 protein level in trophoblast cells induced by LPS. Apelin treatment reduced LPS-induced apoptosis and improved the proliferation, invasion and migration capacities of LPS-mediated trophoblast cells. Additionally, Apelin down-regulated GRP78, p-ASK1 and p-JNK protein levels. The inhibition on LPS-induced trophoblast cell apoptosis and the promotion on invasion and migration by Apelin-36 was counteracted by GRP78 overexpression. To sum up, Apelin-36 could alleviate LPS-induced cell inflammation and apoptosis and improve the invasion and migration of trophoblasts by inhibiting the GRP78/ASK1/JNK signaling.

Effects of cervicothoracic postures on the stiffness of trapezius muscles.

The purposes of this study were to (1) examine the effects of different cervicothoracic postures on the stiffness of trapezius muscles and (2) compare the stiffness of the dominant and non-dominant trapezius muscles. Twenty-one healthy participants joined in this project. After maintaining different cervicothoracic postures for 2 min, MyotonPRO was used to measure the stiffness of the trapezius. The results showed that (1) the stiffness of trapezius muscles was significantly affected by different cervicothoracic postures. With the increase of neck flexion angle, the stiffness of the trapezius muscles increased (p < 0.05). The muscle stiffness of upper back relaxed was higher than that of upper back upright (p < 0.05). (2) The trapezius muscles on the non-dominant side were stiffer than that on the dominant side (p < 0.05). Poor cervicothoracic postures will increase the stiffness of upper, middle and lower trapezius muscles. Keeping the neck and upper back upright will keep the muscle stiffness at a low level, so as to reduce the occurrence of neck and shoulder fatigue and pain.

Fasting blood glucose-to-glycated hemoglobin ratio and all-cause mortality among Chinese in-hospital patients with acute stroke: a 12-month follow-up study.

BACKGROUND: Stroke is a leading cause of death and functional impairment in older people. To assess the prospective association between fasting blood glucose-to-glycated hemoglobin ratio and all-cause mortality and poor prognosis in stroke patients. METHODS: A total of 971 Chinese inpatients with acute stroke (mean age of 65.7) were consecutively enrolled in the prospective clinical study and followed up for 12 months after discharge. Stress hyperglycemia was measured using the ratio of fasting blood glucose (FBG, mmol/L)/glycated hemoglobin (HbA1c, %). The primary outcome was all-cause mortality, and secondary outcomes were poor prognosis defined as infectious complications, a National Institutes of Health Stroke Scale (NIHSS) score ≥ 6, a Barthel Index score ≤ 60, or a modified Rankin Scale (mRS) score of 3-6, presented as multivariate-adjusted odds ratios (ORs) with 95% confidence intervals (CIs) across the quartiles of the FBG/HbA1c ratio. RESULTS: There were 35 (4.1%) all-cause deaths at 3 months and 85 (11.4%) at 12 months. The inpatients with the highest quartile of the FBG/HbA1c ratio had a higher risk of all-cause death at 3 months (adjusted OR: 5.16, 95% CI: 1.03-25.74) and at 12 months (adjusted OR: 2.59, 95% CI: 1.14-5.89)) and a higher risk of infectious complications (adjusted OR 2.37, 95% CI 1.27-4.43) and dysfunction (adjusted OR 1.79, 95% CI 1.06-3.01) during hospitalization than inpatients with the lowest quartile. CONCLUSIONS: Stress hyperglycemia, measured by the FBG/HbA1c ratio, was associated with an increased risk of adverse outcomes, including all-cause death, infectious complications, and dysfunction after stroke.

A prospective epidemiological analysis of controlling nutritional status score with the poor functional outcomes in Chinese patients with haemorrhagic stroke.

Nutritional Risk Screening index is a standard tool to assess nutritional risk, but epidemiological data are scarce on controlling nutritional status (CONUT) as a prognostic marker in acute haemorrhagic stroke (AHS). We aimed to explore whether the CONUT may predict a 3-month functional outcome in AHS. In total, 349 Chinese patients with incident AHS were consecutively recruited, and their malnutrition risks were determined using a high CONUT score of ≥ 2. The cohort patients were divided into high-CONUT (≥ 2) and low-CONUT (< 2) groups, and primary outcomes were a poor functional prognosis defined as the modified Rankin Scale (mRS) score of ≥ 3 at post-discharge for 3 months. Odds ratios (OR) with 95 % confidence intervals (CI) for the poor functional prognosis at post-discharge were estimated by using a logistic analysis with additional adjustments for unbalanced variables between the high-CONUT and low-CONUT groups. A total of 328 patients (60·38 ± 12·83 years; 66·77 % male) completed the mRS assessment at post-discharge for 3 months, with 172 patients at malnutrition risk at admission and 104 patients with a poor prognosis. The levels of total cholesterol and total lymphocyte counts were significantly lower in high-CONUT patients than low-CONUT patients (P = 0·012 and < 0·001, respectively). At 3-month post discharge, there was a greater risk for the poor outcome in the high-CONUT compared with the low-CONUT patients at admission (OR: 2·32, 95 % CI: 1·28, 4·17). High-CONUT scores independently predict a 3-month poor prognosis in AHS, which helps to identify those who need additional nutritional managements.

CXCL14 facilitates the growth and metastasis of ovarian carcinoma cells via activation of the Wnt/ß-catenin signaling pathway.

BACKGROUND: There is an urgent need to identify potential targets in anticancer therapy to improve the survival and prognosis of patients with ovarian cancer (OC). Herein, we investigated the functional significance of chemokine (C-X-C motif) ligand 14 (CXCL14) in OC cell growth and epithelial-mesenchymal transition (EMT). METHODS: qRT PCR and western blotting was used to detect CXCL14 mRNA level and protein expression, respectively. The functional mechanism of CXCL14 in OC was investigated by CCK-8, colony formation and transwell assays. The migration ability of OC cell was determined using wound healing. The protein expressions of CXCL14 and ß-catenin in OC tissues were determined by immumohistochemical staining. RESULTS: We demonstrated that high levels of CXCL14 were associated with a worse prognosis in patients with OC. CXCL14 knockdown considerably restrained the growth, migration and invasion of OC cell in vitro. In contrast, ectopic CXCL14 overexpression yielded the opposite results. Investigations to determine the underlying molecular mechanisms revealed that the Wnt/ß-catenin signaling pathway is involved in CXCL14-facilitated OC cell invasiveness. CONCLUSION: These data collectively demonstrate that CXCL14 contributes to OC cell growth and metastatic potential by regulating the Wnt/ß-catenin signaling pathway.

An Experimental Protocol for Evaluating Pulse Width Modulation Ranges of Evoked Tactile Sensory Feedback in Amputees.

The objective of this study is to develop an experimental protocol to define the range of modulation for different sensory modalities elicited by transcutaneous electrical nerve stimulation (TENS) in amputees with evoked tactile sensation (ETS). Modulation ranges of sensory modalities, such as vibration, buzz, tingling etc., are essential for designing a coding strategy for incoming sensory information from prosthetic hands for each amputee. Here, the modulation ranges of different modalities in pulse width at fixed stimulus frequencies were evaluated. Four healthy subjects and three transradial amputee subjects were recruited to participate in this preliminary test. A single skin site in healthy subjects and five finger areas of the projected finger map (PFM) on the stump skin in amputee subjects were stimulated for evaluation. Then, a finger identification test was conducted to show the feasibility of this sensory coding strategy in one amputee subject. The sensitivity of different sensory modalities was also measured to quantify the minimum pulse width change that subject could distinguish. Results showed that vibration and buzz sensations had wider modulation ranges in pulse width for both healthy and amputee subjects at 20Hz and 50Hz of stimulation, respectively. The average accuracy of finger identification was 91.66% in the amputee subject. The minimum pulse width changes distinguishable for both vibration and buzz sensation were below 20 (us). Results indicated that the protocol of evaluating pulse width modulation ranges for different sensory modalities was effective, and the coding strategy could provide accurate finger-specific sensory information for amputees with ETS.Clinical Relevance- This protocol establishes a guideline for customizing the coding strategy of evoked tactile sensory feedback for each amputee.

Being at risk of malnutrition predicts poor outcomes at 3 months in acute ischemic stroke patients.

BACKGROUND: Malnutrition is confirmed to be associated with poor outcomes in stroke patients. The present study aimed to confirm that being at risk of malnutrition assessed by Nutritional Risk Screening Tool 2002 (NRS-2002) and the Controlling Nutritional Status (CONUT) score predicts poor outcomes at 3 months in acute ischemic stroke (AIS) patients. METHODS: In total, 682 patients with AIS were recruited within 7 days of stroke onset consecutively and 110 were dropped out. They were screened for risk of malnutrition using NRS-2002 and the CONUT score. The primary outcome is the follow-up modified Rankin Scale (mRS) score. Poor outcomes were defined as an (mRS) score ≥ 3 at 3 months post discharge. RESULTS: There was a significant difference in the mRS score at 3 months between patients at risk of malnutrition compared to those not at risk assessed by NRS-2002(P < 0.001) and CONUT (P = 0.011). The logistic regression model showed that the risk of malnourishment (according to NRS-2002), low risk of malnourishment (according to CONUT), and the moderate-to-severe risk of malnourishment (according to CONUT) were associated with higher risk of poor outcomes at 3 months (P < 0.001, P = 0.033, and P = 0.007). The multivariate logistic regression model (adjusted for confounding factors) demonstrated that the risk of malnourishment, according to the NRS-2002, was associated with the increasing risk of poor outcomes at 3 months (odds ratio = 2.31; 95% CI: 1.24-4.30; P = 0.008). CONCLUSIONS: The risk of malnutrition assessed by NRS-2002 and CONUT can predict poor outcomes at 3 months in AIS patients. NRS-2002 is superior to CONUT in predicting poor outcomes at 3 months.

Global vegetation productivity responses to the West Pacific Warm Pool.

Sea surface temperatures (SSTs) strongly influence atmospheric circulation and the Earth's climate, which in turn significantly affects vegetation productivity. Most of the previous studies on the subject have focused on links between the El Niño-Southern Oscillation (ENSO) and vegetation productivity, but few studies have addressed the effects of West Pacific Warm Pool (WPWP) on that although the early stages of the ENSO phenomenon may first develop there. In this paper, we use the mean SST values in the WPWP to construct a climate index, known as the WPWP index (WPI), and study the impacts of the WPWP on global vegetation productivity. We provide evidence for a robust link among the alternating warm and cool WPI pattern, terrestrial vegetation productivity and carbon balance. The analysis is based on both satellite observations and model simulations. The results of this study show that the warm and cool WPWP phases have inverse effects on land surface temperature and precipitation. A warm (cool) WPWP is associated with a warmer (cooler) climate on global land surfaces as well as a drier (wetter) climate in southern hemisphere, and hence enhances (suppresses) vegetation productivity in the latitudes of approximately 10-70°N and suppresses (enhances) vegetation growth in the latitudes of approximately 10-30°S. The underlying mechanism is also discussed. The WPI serves as a meaningful climate index for studying the ocean-vegetation teleconnections.

Neural Correlation between Evoked Tactile Sensation and Central Activities in the Somatosensory Cortex.

Evoked tactile sensation (ETS) is induced with stimulation of areas in the projected finger map (PFM) in the stump skin of forearm amputees. The aim of the present study is to further explore the neural correlation of the ETS with central activities in the somatosensory cortex (SI). Two forearm amputees were recruited to participate in this study. The neuroimaging technique of Magnetoencephalography (MEG) was employed to reveal the activities in the somatosensory cortex (SI), while the thumb and little finger areas in the PFM and the thumb and little finger of the contralateral hand were stimulated with a bi-phasic current pulse train. In one subject, local anesthesia was applied to the skin areas of the thumb and little finger of the PFM to examine the effects of blocking peripheral nerve transmission on the central activities in SI. Results obtained in the two subjects indicated that stimulation of the thumb and little finger areas in the PFM of amputated side produced the similar neural activities in the somatosensory cortex as those of stimulating the thumb and little finger of the contralateral hand, both of which were consistent with the homunculus organization of the SI cortex. The intensity of SI cortical activities was proportional to the intensity of the amplitude of peripheral stimulation. In particular, local anesthesia reduced the intensity of central activities in SI as revealed by the MEG response, as well as the sensitivity of ETS as reported by the subject. This neural correlation appears to suggest that the finger areas in the PFM in the stump skin are neuroanatomically connected to the finger areas of the somatosensory cortex. Thus, electrical stimulation of the PFM can induce natural sensation as that of normal fingers. This establishes the neural basis of natural sensory feedback from the prosthetic hand to the forearm amputee with finger-to-finger specificity.

Inhibition of Parkinsonian tremor with cutaneous afferent evoked by transcutaneous electrical nerve stimulation.

BACKGROUND: Recent study suggests that tremor signals are transmitted by way of multi-synaptic corticospinal pathway. Neurophysiological studies have also demonstrated that cutaneous afferents exert potent inhibition to descending motor commands by way of spinal interneurons. We hypothesize in this study that cutaneous afferents could also affect the transmission of tremor signals, thus, inhibit tremor in patients with PD. METHODS: We tested this hypothesis by activating cutaneous afferents in the dorsal hand skin innervated by superficial radial nerve using transcutaneous electrical nerve stimulation (TENS). Eight patients with PD having tremor dominant symptom were recruited to participate in this study using a consistent experimental protocol for tremor inhibition. Resting tremor and electromyogram (EMG) of muscles in the upper extremity of these subjects with PD were recorded, while surface stimulation was applied to the dorsal skin of the hand. Fifteen seconds of data were recorded for 5 s prior to, during and post stimulation. Power spectrum densities (PSDs) of tremor and EMG signals were computed for each data segment. The peak values of PSDs in three data segments were compared to detect evidence of tremor inhibition. RESULTS: At stimulation intensity from 1.5 to 1.75 times of radiating sensation threshold, apparent suppressions of tremor at wrist, forearm and upper arm and in the EMGs were observed immediately at the onset of stimulation. After termination of stimulation, tremor and rhythmic EMG bursts reemerged gradually. Statistical analysis of peak spectral amplitudes showed a significant difference in joint tremors and EMGs during and prior to stimulation in all 8 subjects with PD. The average percentage of suppression was 61.56% in tremor across all joints of all subjects, and 47.97% in EMG of all muscles. The suppression appeared to occur mainly in distal joints and muscles. There was a slight, but inconsistent effect on tremor frequency in the 8 patients with PD tested. CONCLUSIONS: Our results provide direct evidence that tremor in the upper extremity of patients with PD can be inhibited to a large extent with evoked cutaneous reflexes via surface stimulation of the dorsal hand skin area innervated by the superficial radial nerve.

Neural computational modeling reveals a major role of corticospinal gating of central oscillations in the generation of essential tremor.

Essential tremor, also referred to as familial tremor, is an autosomal dominant genetic disease and the most common movement disorder. It typically involves a postural and motor tremor of the hands, head or other part of the body. Essential tremor is driven by a central oscillation signal in the brain. However, the corticospinal mechanisms involved in the generation of essential tremor are unclear. Therefore, in this study, we used a neural computational model that includes both monosynaptic and multisynaptic corticospinal pathways interacting with a propriospinal neuronal network. A virtual arm model is driven by the central oscillation signal to simulate tremor activity behavior. Cortical descending commands are classified as alpha or gamma through monosynaptic or multisynaptic corticospinal pathways, which converge respectively on alpha or gamma motoneurons in the spinal cord. Several scenarios are evaluated based on the central oscillation signal passing down to the spinal motoneurons via each descending pathway. The simulated behaviors are compared with clinical essential tremor characteristics to identify the corticospinal pathways responsible for transmitting the central oscillation signal. A propriospinal neuron with strong cortical inhibition performs a gating function in the generation of essential tremor. Our results indicate that the propriospinal neuronal network is essential for relaying the central oscillation signal and the production of essential tremor.

Effects of glycinin basic polypeptide on sensory and physicochemical properties of chilled pork.

Effects of glycinin basic polypeptide (GBP) on sensory and physicochemical properties of pork during chilled storage were investigated. Pork treated with GBP was analyzed periodically for sensory properties, pH, total volatile base nitrogen (TVB-N), α-thiobarbituric acid (TBA), and total viable count (TVC) values. Compared with controls, TBA values of pork treated with GBP did not change. TVB-N, pH, and TVC values of pork showed reductions with increasing concentrations of GBP during 8 days of storage. However, there were increases in sensory scores. TVC values of treated pork showed a positive linear relationship with both pH and TVB-N values. GBP at 0.16 and 0.20% efficiently inhibited bacterial growth, and enhanced chilled pork sensory scores. Therefore, GBP has potential as a pork biological preservative for extension of shelf life during chilled storage.

Contribution of inter-muscular synchronization in the modulation of tremor intensity in Parkinson's disease.

BACKGROUND: Involuntary central oscillations at single and double tremor frequencies drive the peripheral neuromechanical system of muscles and joints to cause tremor in Parkinson's disease (PD). The central signal of double tremor frequency was found to correlate more directly to individual muscle EMGs (Timmermann et al. 2003). This study is aimed at investigating what central components of oscillation contribute to inter-muscular synchronization in a group of upper extremity muscles during tremor in PD patients. METHODS: 11 idiopathic, tremor dominant PD subjects participated in this study. Joint kinematics during tremor in the upper extremity was recorded along with EMGs of six upper arm muscles using a novel experimental apparatus. The apparatus provided support for the upper extremity on a horizontal surface with reduced friction, so that resting tremor in the arm can be recorded with a MotionMonitor II system. In each subject, the frequencies of rhythmic firings in upper arm muscles were determined using spectral analysis. Paired and pool-averaged coherence analyses of EMGs for the group of muscles were performed to correlate the level of inter-muscular synchronization to tremor amplitudes at shoulder and elbow. The phase shift between synchronized antagonistic muscle pairs was calculated to aid coherence analysis in the muscle pool. RESULTS: Recorded EMG revealed that rhythmic firings were present in most recorded muscles, which were either synchronized to form phase-locked bursting cycles at a subject specific frequency, or unsynchronized with a random phase distribution. Paired coherence showed a stronger synchronization among a subset of recorded arm muscles at tremor frequency than that at double tremor frequency. Furthermore, the number of synchronized muscles in the arm was positively correlated to tremor amplitudes at elbow and shoulder. Pool-averaged coherence at tremor frequency also showed a better correlation with the amplitude of resting tremor than that of double tremor frequency, indicating that the neuromechanical coupling in peripheral neuromuscular system was stronger at tremor frequency. CONCLUSIONS: Both paired and pool-averaged coherences are more consistent indexes to correlate to tremor intensity in a group of upper extremity muscles of PD patients. The central drive at tremor frequency contributes mainly to synchronize peripheral muscles in the modulation of tremor intensity.

Identification of genes involved in the phosphate metabolism in Cryptococcus neoformans.

Cryptococcus neoformans is a pathogenic basidiomycetous yeast that can cause life-threatening meningoencephalitis in immuno-compromized patients. To propagate in the human body, this organism has to acquire phosphate that functions in cellular signaling pathways and is also an essential component of nucleic acids and phospholipids. Thus it is reasonable to assume that C. neoformans (Cn) possesses a phosphate regulatory system (PHO system) analogous to that of other fungi. By BLAST searches using the amino acid sequences of the components of the PHO system of Saccharomyces cerevisiae (Sc), we found potential counterparts to ScPHO genes in C. neoformans, namely, acid phosphatase (CnPHO2), the cyclin-dependent protein kinase (CDK) inhibitor (CnPHO81), Pho85-cyclin (CnPHO80), and CDK (CnPHO85). Disruption of each candidate gene, except CnPHO85, followed by phenotypic analysis, identified most of the basic components of the CnPHO system. We found that CnPHO85 was essential for the growth of C. neoformans, having regulatory function in the CnPHO system. Genetic screening and ChIP analysis, showed that CnPHO4 encodes a transcription factor that binds to the CnPHO genes in a Pi-dependent manner. By RNA-seq analysis of the wild-type and the regulatory mutants of the CnPHO system, we found C. neoformans genes whose expression is controlled by the regulators of the CnPHO system. Thus the CnPHO system shares many properties with the ScPHO system, but expression of those CnPHO genes that encode regulators is controlled by phosphate starvation, which is not the case in the ScPHO system (except ScPHO81). We also could identify some genes involved in the stress response of the pathogenic yeast, but CnPho4 appeared to be responsible only for phosphate starvation.