In solid tumours, cancer cells exist within hypoxic microenvironments, and their metabolic adaptation to this hypoxia is driven by HIF-1 transcription factor, which is overexpressed in a broad range of human cancers. HIF inhibitors are under pre-clinical investigation and clinical trials, but there is evidence that hypoxic cancer cells can adapt metabolically to HIF-1 inhibition, which would provide a potential route for drug resistance. Here, we review accumulating evidence of such adaptions in carbohydrate and creatine metabolism and other HIF-1-independent mechanisms that might allow cancers to survive hypoxia despite anti-HIF-1 therapy. These include pathways in glucose, glutamine, and lipid metabolism; epigenetic mechanisms; post-translational protein modifications; spatial reorganization of enzymes; signalling pathways such as Myc, PI3K-Akt, 2-hyxdroxyglutarate and AMP-activated protein kinase (AMPK); and activation of the HIF-2 pathway. All of these should be investigated in future work on hypoxia bypass mechanisms in anti-HIF-1 cancer therapy. In principle, agents targeted toward HIF-1β rather than HIF-1α might be advantageous, as both HIF-1 and HIF-2 require HIF-1β for activation. However, HIF-1β is also the aryl hydrocarbon nuclear transporter (ARNT), which has functions in many tissues, so off-target effects should be expected. In general, cancer therapy by HIF inhibition will need careful attention to potential resistance mechanisms.
Matched MeSH terms: Adaptation, Physiological/physiology*; Signal Transduction/physiology; Cell Hypoxia/physiology*
Neuromuscular electrical stimulation plays a pivotal role in rehabilitating muscle function among individuals with neurological impairment. However, there remains uncertainty regarding whether the muscle's response to electrical excitation is affected by forearm posture, joint angle, or a combination of both factors. This study aimed to investigate the effects of forearm postures and elbow joint angles on the muscle torque and MMG signals. Measurements of the torque around the elbow and MMG of the biceps brachii (BB) muscle were conducted in 36 healthy subjects (age, 22.24 ± 2.94 years; height, 172 ± 0.5 cm; and weight, 67.01 ± 7.22 kg) using an in-house elbow flexion testbed and neuromuscular electrical stimulation (NMES) of the BB muscle. The BB muscle was stimulated while the forearm was positioned in the neutral, pronation, or supination positions. The elbow was flexed at angles of 10°, 30°, 60°, and 90°. The study analyzed the impact of the forearm posture(s) and elbow joint angle(s) on the root-mean-square value of the torque (TQRMS). Subsequently, various MMG parameters, such as the root-mean-square value (MMGRMS), the mean power frequency (MMGMPF), and the median frequency (MMGMDF), were analyzed along the longitudinal, lateral, and transverse axes of the BB muscle fibers. The test-retest interclass correlation coefficient (ICC21) for the torque and MMG ranged from 0.522 to 0.828. Repeated-measure ANOVAs showed that the forearm posture and elbow flexion angle significantly influenced the TQRMS (p < 0.05). Similarly, the MMGRMS, MMGMPF, and MMGMDF showed significant differences among all the postures and angles (p < 0.05). However, the combined main effect of the forearm posture and elbow joint angle was insignificant along the longitudinal axis (p > 0.05). The study also found that the MMGRMS and TQRMS increased with increases in the joint angle from 10° to 60° and decreased at greater angles. However, during this investigation, the MMGMPF and MMGMDF exhibited a consistent decrease in response to increases in the joint angle for the lateral and transverse axes of the BB muscle. These findings suggest that the muscle contraction evoked by NMES may be influenced by the interplay between actin and myosin filaments, which are responsible for muscle contraction and are, in turn, influenced by the muscle length. Because restoring the function of limbs is a common goal in rehabilitation services, the use of MMG in the development of methods that may enable the real-time tracking of exact muscle dimensional changes and activation levels is imperative.
In photosynthesis, a very small amount of the solar energy absorbed is transformed into chemical energy, while the rest is wasted as heat and fluorescence. This excess energy can be harvested through biophotovoltaic platforms to generate electrical energy. In this study, algal biofilms formed on ITO anodes were investigated for use in the algal biophotovoltaic platforms. Sixteen algal strains, comprising local isolates and two diatoms obtained from the Culture Collection of Marine Phytoplankton (CCMP), USA, were screened and eight were selected based on the growth rate, biochemical composition and photosynthesis performance using suspension cultures. Differences in biofilm formation between the eight algal strains as well as their rapid light curve (RLC) generated using a pulse amplitude modulation (PAM) fluorometer, were examined. The RLC provides detailed information on the saturation characteristics of electron transport and overall photosynthetic performance of the algae. Four algal strains, belonging to the Cyanophyta (Cyanobacteria) Synechococcus elongatus (UMACC 105), Spirulina platensis. (UMACC 159) and the Chlorophyta Chlorella vulgaris (UMACC 051), and Chlorella sp. (UMACC 313) were finally selected for investigation using biophotovoltaic platforms. Based on power output per Chl-a content, the algae can be ranked as follows: Synechococcus elongatus (UMACC 105) (6.38×10(-5) Wm(-2)/µgChl-a)>Chlorella vulgaris UMACC 051 (2.24×10(-5) Wm(-2)/µgChl-a)>Chlorella sp.(UMACC 313) (1.43×10(-5) Wm(-2)/µgChl-a)>Spirulina platensis (UMACC 159) (4.90×10(-6) Wm(-2)/µgChl-a). Our study showed that local algal strains have potential for use in biophotovoltaic platforms due to their high photosynthetic performance, ability to produce biofilm and generation of electrical power.
A trial was conducted to determine the influence of short-term exposure to high ambient temperature at 28 and 35 days of age on deep body temperatures (Tb) and subsequent growth of birds until 42 days of age. A total of 90 day old chicks were reared in stainless steel battery cages and were assigned at random into 18 pens of 5 birds each, with 9 pens containing males and another 9 pens containing females. Three treatment groups, each represented by 3 male and 3 female pens, were represented by T1 without any heat exposure, T2 with heat exposure starting at day 28 and T3 with heat exposure starting at day 35. Heat stress was defined as 180 min exposure to 35 +/- 1 degrees C. Tb and body weights were measured at 35, 37 and 39 days of age immediately following heat exposure. Heat stress resulted in higher Tb and Onset of heat stress at 28 days resulted in significantly lower Tb than onset of heat stress at 35 days. Lower Tb in T2 than T3 permitted recovery in body weight at 42 days. Sexes responded similarly to heat stress.
Matched MeSH terms: Aging/physiology*; Body Temperature Regulation/physiology*; Chickens/physiology*
Technique-specific high-intensity interval training (HIITTS) has been proven to be an effective method to enhance the sport-specific bio-motor abilities of taekwondo athletes. However, studies regarding its effects on comprehensive measures of cardiorespiratory fitness are limited. Furthermore, there is a lack of clarity regarding the extent of individual adaptations to this method compared to HIIT in the form of repeated sprints (HIITRS). This study compared the individual adaptations to HIITRS and HIITTS on cardiorespiratory fitness and anaerobic power in trained taekwondo athletes (age = 19.8 ± 1.3 years; body mass = 75.4 ± 9.1 kg; height = 1.73 ± 0.0 .m). All participants completed three sessions per week of a 60-minute regular taekwondo training. Following the 60-minute training, participants completed 3 sets of 10 × 4 s all-out HIITRS or same sets of repeated kicks with both legs (HIITTS) over a 6-week training period. In both groups, rest intervals were set at 15 seconds between efforts and one minute between sets. Before and after the training period, participants underwent a series of lab- and field-based tests to evaluate cardiorespiratory fitness and bio-motor abilities. Both interventions resulted in significant improvements in maximum oxygen uptake (V̇O2max), O2 pulse (V̇O2/HR), first ventilatory threshold (VT1), second ventilatory threshold (VT2), cardiac output (Q̇max), stroke volume (SV), peak power output (PPO), average power output (APO), squat jump (SJ), and countermovement jump (CMJ). However, linear speed (20-m speed time) and taekwondo-specific agility test (TSAT) only responded to HIITRS. HIITRS resulted in greater changes in V̇O2max, V̇O2/HR, VT2, and Q̇max, and higher percentage of responders in measured parameters than HIITTS. In addition, HIITRS elicited lower inter-individual variability (CV) in percent changes from pre- to post-training in all measured variables. These results suggest that incorporating 3 sessions per week of HIITRS into regular taekwondo training results in significantly greater and more homogenized adaptations in cardiorespiratory fitness and bio-motor abilities than HIITTS among trained taekwondo athletes.
This study aimed to explore the impact of functional training on the physical fitness of young elite field hockey players. The study comprised 40 young elite male field hockey players with the following characteristics (mean ± SD age: 21.5 ± 0.8 years; height: 176.9 ± 2.6 cm; weight: 68.4 ± 5.1 kg; BMI: 21.8 ± 1.3; training experience: 51.2 ± 5.4 months). Twenty participants were allocated to two groups: the functional training group (FTG) and the control training group (CG). Each group received 60-minute training sessions three times per week for 12 weeks. Generalized estimating equation analysis and a Bonferroni test for pairwise comparisons were used to assess the intervention's efficacy. Before the start of the exercise program, no statistically significant differences were observed in physical fitness measures between the FTG and CG (p > 0.05). However, by the sixth week, a significant difference appeared in both the T-Agility test (p < 0.001) and endurance (p = 0.024) between the two groups, while no notable distinctions were detected in other fitness parameters (p > 0.05). After a 12-week training program, the FTG demonstrated improvements in all physical fitness measures [flexibility (p < 0.001); Illinois agility test (p < 0.001); T-agility test (p = 0.020); endurance (p < 0.001)] except speed, which exhibited no significant impact (p = 0.175). Notable enhancements in T-agility and endurance were evident after just six weeks of functional training, and a 12-week functional training regimen showed superiority over standard training approaches in young elite male field hockey players. These findings encourage the efficacy of functional training exercises over traditional methods in enhancing athletes' fitness parameters.
Handwriting is an outstanding case of a highly complex and efficient fine motor skill. However, little is known about its neural underpinnings during continuous handwriting production. In the present study, we examined the effects of orthographic character complexity (i.e. the stroke number of a Chinese character) on both neural and behavioural activities during an EEG-based naturalistic fluent sentence-handwriting task from 102 adult Chinese native speakers. For each written character, the interval between finishing the preceding character and its onset (inter-character interval) as well as the amplitudes of the onset-synchronized event-related potential (ERP) in pre- and post-onset time windows was defined as dependent variables. The effects of character complexity and other confounding factors were analysed with linear mixed models. Character complexity increased the inter-character interval and significantly affected ERP amplitudes in both pre- and post-onset time windows. The ERP pattern in the pre-event time window exhibited a dipole-like activation in the left motor cortex, and its amplitude increased with character complexity in line with the documented relationship between the lateralized readiness potential and motor complexity. This study demonstrates the feasibility of studying neurocognitive processes in complex naturalistic motor tasks and extends our knowledge about the dynamic pattern of handwriting-related neural activities.
Matched MeSH terms: Motor Cortex/physiology; Motor Skills/physiology; Psychomotor Performance/physiology
Chrononutrition, an emerging body of evidence on the relationship between biological rhythms and metabolism, has been established to be associated with glycemic responses. However, the available evidence is inconsistent, due to protocol variations. Therefore, this review aims to summarize the findings on chrononutrition characteristics and their association with glycemic responses among adults. Systematic searches were conducted across six databases (PubMed, EBSCO Host, ProQuest Central, MEDLINE & Ovid, Scopus and Web of Science) to identify all relevant studies published from January 2012. Two reviewers independently screened the abstracts and full-text articles based on the inclusion and exclusion criteria. Details about population characteristics, study methods and key findings were extracted following the PRISMA-ScR guideline. The quality of selected studies was evaluated using the mixed methods appraisal tool. The searchers identified 49 studies eligible for analysis. The results showed that meal timing, particularly night-time eating and snacking were associated with glycemic responses. Regarding meal regularity, skipping breakfast may affect glycemic responses, but no clear conclusion was drawn about its effect on insulin. The association between meal frequency and glycemic responses was inconclusive. Night fasting duration and restricted eating window are potentially associated with glycemic responses. The current review extensively investigates the association between chrononutrition factors and glycemic responses in adults. However, more prospective cohort and interventional studies are needed to better understand this causal-effect relationship.
The extensive crosstalk between the developing heart and lung is critical to their proper morphogenesis and maturation. However, there remains a lack of models that investigate the critical cardio-pulmonary mutual interaction during human embryogenesis. Here, we reported a novel stepwise strategy for directing the simultaneous induction of both mesoderm-derived cardiac and endoderm-derived lung epithelial lineages within a single differentiation of human-induced pluripotent stem cells (hiPSCs) via temporal specific tuning of WNT and nodal signaling in the absence of exogenous growth factors. Using 3D suspension culture, we established concentric cardio-pulmonary micro-Tissues (μTs), and expedited alveolar maturation in the presence of cardiac accompaniment. Upon withdrawal of WNT agonist, the cardiac and pulmonary components within each dual-lineage μT effectively segregated from each other with concurrent initiation of cardiac contraction. We expect that our multilineage differentiation model will offer an experimentally tractable system for investigating human cardio-pulmonary interaction and tissue boundary formation during embryogenesis.
The use of mesenchymal stem cells (MSCs) for cartilage repair has generated much interest owing to their multipotentiality. However, their significant presence in peripheral blood (PB) has been a matter of much debate. The objectives of this study are to isolate and characterize MSCs derived from PB and, compare their chondrogenic potential to MSC derived from bone marrow (BM). PB and BM derived MSCs from 20 patients were isolated and characterized. From 2 ml of PB and BM, 5.4 ± 0.6 million and 10.5 ± 0.8 million adherent cells, respectively, were obtained by cell cultures at passage 2. Both PB and BM derived MSCs were able to undergo tri-lineage differentiation and showed negative expression of CD34 and CD45, but positively expressed CD105, CD166, and CD29. Qualitative and quantitative examinations on the chondrogenic potential of PB and BM derived MSCs expressed similar cartilage specific gene (COMP) and proteoglycan levels, respectively. Furthermore, the s-GAG levels expressed by chondrogenic MSCs in cultures were similar to that of native chondrocytes. In conclusion, this study demonstrates that MSCs from PB maintain similar characteristics and have similar chondrogenic differentiation potential to those derived from BM, while producing comparable s-GAG expressions to chondrocytes.
In animal models, exposure to high noise levels can cause permanent damage to hair-cell synapses (cochlear synaptopathy) for high-threshold auditory nerve fibers without affecting sensitivity to quiet sounds. This has been confirmed in several mammalian species, but the hypothesis that lifetime noise exposure affects auditory function in humans with normal audiometric thresholds remains unconfirmed and current evidence from human electrophysiology is contradictory. Here we report the auditory brainstem response (ABR), and both transient (stimulus onset and offset) and sustained functional magnetic resonance imaging (fMRI) responses throughout the human central auditory pathway across lifetime noise exposure. Healthy young individuals aged 25-40 years were recruited into high (n = 32) and low (n = 30) lifetime noise exposure groups, stratified for age, and balanced for audiometric threshold up to 16 kHz fMRI demonstrated robust broadband noise-related activity throughout the auditory pathway (cochlear nucleus, superior olivary complex, nucleus of the lateral lemniscus, inferior colliculus, medial geniculate body and auditory cortex). fMRI responses in the auditory pathway to broadband noise onset were significantly enhanced in the high noise exposure group relative to the low exposure group, differences in sustained fMRI responses did not reach significance, and no significant group differences were found in the click-evoked ABR. Exploratory analyses found no significant relationships between the neural responses and self-reported tinnitus or reduced sound-level tolerance (symptoms associated with synaptopathy). In summary, although a small effect, these fMRI results suggest that lifetime noise exposure may be associated with central hyperactivity in young adults with normal hearing thresholds.
Pollinator syndrome is one of the most important determinants regulating pollen dispersal in tropical tree species. It has been widely accepted that the reproduction of tropical forest species, especially dipterocarps that rely on insects with weak flight for their pollination, is positively density-dependent. However differences in pollinator syndrome should affect pollen dispersal patterns and, consequently, influence genetic diversity via the mating process. We examined the pollen dispersal pattern and mating system of Shorea maxwelliana, the flowers of which are larger than those of Shorea species belonging to section Mutica which are thought to be pollinated by thrips (weak flyers). A Bayesian mating model based on the paternity of seeds collected from mother trees during sporadic and mass flowering events revealed that the estimated pollen dispersal kernel and average pollen dispersal distance were similar for both flowering events. This evidence suggests that the putative pollinators - small beetles and weevils - effectively contribute to pollen dispersal and help to maintain a high outcrossing rate even during sporadic flowering events. However, the reduction in pollen donors during a sporadic event results in a reduction in effective pollen donors, which should lead to lower genetic diversity in the next generation derived from seeds produced during such an event. Although sporadic flowering has been considered less effective for outcrossing in Shorea species that depend on thrips for their pollination, effective pollen dispersal by the small beetles and weevils ensures outcrossing during periods of low flowering tree density, as occurs in a sporadic flowering event.
An N-acylhomoserine lactone (AHL)-degrading bacterial strain, L62, was isolated from a sample of fermentation brine of Chinese soya sauce by using rich medium agar supplemented with soya sauce (10% v/v). L62, a rod-shaped Gram positive bacterium with amylolytic activity, was phylogentically related to Bacillus sonorensis by 16S ribosomal DNA and rpoB sequence analyses. B. sonorensis L62 efficiently degraded N-3-oxohexanoyl homoserine lactone and N-octanoylhomoserine lactone. However, the aiiA homologue, encoding an autoinducer inactivation enzyme catalyzing the degradation of AHLs, was not detected in L62, suggesting the presence of a different AHL-degrading gene in L62. To the best of our knowledge, this is the first report of AHL-degrading B. sonorensis from soya sauce liquid state fermentation.
In this paper, a personal verification method using finger vein is presented. Finger vein can be considered more secured compared to other hands based biometric traits such as fingerprint and palm print because the features are inside the human body. In the proposed method, a new texture descriptor called local line binary pattern (LLBP) is utilized as feature extraction technique. The neighbourhood shape in LLBP is a straight line, unlike in local binary pattern (LBP) which is a square shape. Experimental results show that the proposed method using LLBP has better performance than the previous methods using LBP and local derivative pattern (LDP).
Seven species of Mycena are reported as luminescent, representing specimens collected in Belize, Brazil, Dominican Republic, Jamaica, Japan (Bonin Islands), Malaysia (Borneo) and Puerto Rico. Four of them represent new species (Mycena luxaeterna, M. luxarboricola, M. luxperpetua, M. silvaelucens) and three represent new reports of luminescence in previously described species (M. aff. abieticola, M. aspratilis, M. margarita). Mycena subepipterygia is synonymized with M. margarita, and M. chlorinosma is proposed as a possible synonym. Comprehensive descriptions, illustrations, photographs and comparisons with phenetically similar species are provided. A redescription of M. chlorophos, based on analyses of type specimens and recently collected topotypical material, is provided. The addition of these seven new or newly reported luminescent species of Mycena brings the total to 71 known bioluminescent species of fungi.