Osteocyte Egln1/Phd2 links oxygen sensing and biomineralization via FGF23

Osteocytes act within a hypoxic environment to control key steps in bone formation.FGF23,a critical phosphate-regulating hormone,is stimulated by low oxygen/iron in acute and chronic diseases,however the molecular mechanisms directing this process remain unclear.Our goal was to identify the osteocyte factors responsible for FGF23 production driven by changes in oxygen/iron utilization.Hypoxia-inducible factor-prolyl hydroxylase inhibitors(HIF-PHI)which stabilize HIF transcription factors,increased Fgf23 in normal mice,as well as in osteocyte-like cells;in mice with conditional osteocyte Fgf23 deletion,circulating i FGF23 was suppressed.An inducible MSC cell line(‘MPC2’)underwent FG-4592 treatment and ATACseq/RNAseq,and demonstrated that differentiated osteocytes significantly increased HIF genomic accessibility versus progenitor cells.Integrative genomics also revealed increased prolyl hydroxylase Egln1(Phd2)chromatin accessibility and expression,which was positively associated with osteocyte differentiation.In mice with chronic kidney disease(CKD),Phd1-3 enzymes were suppressed,consistent with FGF23 upregulation in this model.Conditional loss of Phd2 from osteocytes in vivo resulted in upregulated Fgf23,in line with our findings that the MPC2 cell line lacking Phd2(CRISPR Phd2-KO cells)constitutively activated Fgf23 that was abolished by HIF1αblockade.In vitro,Phd2-KO cells lost iron-mediated suppression of Fgf23 and this activity was not compensated for by Phd1 or-3.In sum,osteocytes become adapted to oxygen/iron sensing during differentiation and are directly sensitive to bioavailable iron.Further,Phd2 is a critical mediator of osteocyte FGF23 production,thus our collective studies may provide new therapeutic targets for skeletal diseases involving disturbed oxygen/iron sensing.

Warmer temperature during asexual reproduction induce methylome, transcriptomic, and lasting phenotypic changes in Fragaria vesca ecotypes

Plants must adapt with increasing speed to global warming to maintain their fitness.One rapid adaptation mechanism is epigenetic memory,which may provide organisms sufficient time to adapt to climate change.We studied how the perennial Fragaria vesca adapted to warmer temperatures(28◦C vs.18◦C)over three asexual generations.Differences in flowering time,stolon number,and petiole length were induced by warmer temperature in one or more ecotypes after three asexual generations and persisted in a common garden environment.Induced methylome changes differed between the four ecotypes from Norway,Iceland,Italy,and Spain,but shared methylome responses were also identified.Most differentially methylated regions(DMRs)occurred in the CHG context,and most CHG and CHH DMRs were hypermethylated at the warmer temperature.In eight CHG DMR peaks,a highly similar methylation pattern could be observed between ecotypes.On average,13%of the differentially methylated genes between ecotypes also showed a temperature-induced change in gene expression.We observed ecotype-specific methylation and expression patterns for genes related to gibberellin metabolism,flowering time,and epigenetic mechanisms.Furthermore,we observed a negative correlation with gene expression when repetitive elements were found near(±2 kb)or inside genes.In conclusion,lasting phenotypic changes indicative of an epigenetic memory were induced by warmer temperature and were accompanied by changes in DNA methylation patterns.Both shared methylation patterns and transcriptome differences between F.vesca accessions were observed,indicating that DNA methylation may be involved in both general and ecotype-specific phenotypic variation.

A Sensor Network Coverage Planning Based on Adjusted Single Candidate Optimizer

Wireless sensor networks(WSNs)are widely used for various practical applications due to their simplicity and versatility.The quality of service in WSNs is greatly influenced by the coverage,which directly affects the monitoring capacity of the target region.However,low WSN coverage and uneven distribution of nodes in random deployments pose significant challenges.This study proposes an optimal node planning strategy for net-work coverage based on an adjusted single candidate optimizer(ASCO)to address these issues.The single candidate optimizer(SCO)is a metaheuristic algorithm with stable implementation procedures.However,it has limitations in avoiding local optimum traps in complex node coverage optimization scenarios.The ASCO overcomes these limitations by incorporating reverse learning and multi-direction strategies,resulting in updated equations.The performance of the ASCO algorithm is compared with other algorithms in the literature for optimal WSN node coverage.The results demonstrate that the ASCO algorithm offers efficient performance,rapid convergence,and expanded coverage capabilities.Notably,the ASCO achieves an archival coverage rate of 88%,while other approaches achieve coverage rates below or equal to 85%under the same conditions.

Randomized control trial of a culturally adapted behavioral activation therapy for Muslim patients with depression in Pakistan

BACKGROUND Behavioral activation therapy(BA)is as effective as cognitive behavior therapy(CBT)in treating depression and can be delivered by practitioners with much less psychological training,making it particularly suitable for low resource settings.BA that is culturally adapted for Muslims(BA-M)is a culturally adapted form of BA that has been found acceptable and feasible for Muslims with depression in the United Kingdom and Turkey;however,this is the first time that its efficacy has been determined through a definitive randomized controlled trial.AIM To compare the effectiveness of BA-M with CBT for Muslim patients with depression in Pakistan.METHODS One hundred and eight patients were randomized 1:1 to treatment arms in a parallel-group randomized controlled trial in hospital or community sites in Lahore,Pakistan.Recruitment followed self-referral or referrals from clinicians,consultants or relevant professionals at each site.Four measures were recorded by blinded assessors:The patient health questionnaire-9(PHQ-9);the BA for depression scale short form(BADS-SF);symptom checklist-revised and the World Health Organization Quality-of-Life Brief Scale.All measures were recorded at baseline and post treatment;PHQ-9 and BADS-SF were also recorded at each session and at three month follow up.The primary analysis was to regress the PHQ-9 score after therapy upon the PHQ-9 score before therapy(baseline)and the type of therapy given,that is,analysis of covariance.In addition,analysis using PHQ-9 scores collected at each therapy session was employed in a 2-level regression model.RESULTS Patients in the BA-M arm experienced greater improvement in PHQ-9 score of 1.95 units compared to the CBT arm after adjusting for baseline values(P=0.006)The key reason behind this improvement was that patients were retained in therapy longer under BA-M,in which patients were retained for an average 0.75 sessions more than CBT patients(P=0.013).Patients also showed significant differences on physical(P<0.001),psychological(P=0.004)and social(P=0.047)domains of Quality of Life(QoL)at post treatment level,indicating an increased QoL in the BA-M group as compared to the treatment as usual group.Some baseline differences were noted in both groups for BA scores and two domains of QoL scale:Physical and environment,which might have influenced the results,though the BA-M group showed more improvement at completion of therapy.CONCLUSION Results proved the efficacy of BA-M in reducing symptoms for depressed patients in Pakistan,indicating BA-M is a promising treatment modality for depression in future,particularly in low resource settings.

Adapted Metrics for a Modified Coulomb/Newton’s Potential

Modified Theories of Gravity include spin dependence in General Relativity, to account for additional sources of gravity instead of dark matter/energy approach. The spin-spin interaction is already included in the effective nuclear force potential, and theoretical considerations and experimental evidence hint to the hypothesis that Gravity originates from such an interaction, under an averaging process over spin directions. This invites to continue the line of theory initiated by Einstein and Cartan, based on tetrads and spin effects modeled by connections with torsion. As a first step in this direction, the article considers a new modified Coulomb/Newton Law accounting for the spin-spin interaction. The physical potential is geometrized through specific affine connections and specific semi-Riemannian metrics, canonically associated to it, acting on a manifold or at the level of its tangent bundle. Freely falling particles in these “toy Universes” are determined, showing an interesting behavior and unexpected patterns.

Preliminary Results of Dementia Prevalence among Elderly People at Home by Cognitive Disorder Adapted Test of Niamey (Niger)

Introduction: Neurocognitive disorders are frequent with aging and are often seen at advancing stages in our context. It is really difficult to evaluate rapidly Nigerien elderly persons according to tools available on cognitive status while there is a great number of uneducated elderly people who suffer from cognitive deficiency. The purpose was to determine neurocognitive disorders prevalence in uneducated groups and Muslim elderly people by using the cognitive disorder examination (Codex) test adopted in the population living at home in Niamey (Niger). Materials and Methods: These are the results of a preliminary prospective study with simple three (3) random sampling concerning elderly people aged 60 and over living at home in whom the codex test adapted to Niamey was administered in uneducated Muslim elderly people for a total duration of four (4) minutes. This screen-adapted test should be completed by the mini-mental test of Senegal which is adapted globally to uneducated people in hospitals. The basic Codex test was developed in France for educated people, so we used this basic test in our educated people in the same study. Results: A total of 198 patients had been collected, of which 51.5% were female with an average age of 68 years with extremes of 60 to 84 years. 40 were educated. Among educated persons, 62.5% had a very low probability of dementia and 5% had a very high probability of dementia in the first step of the Codex. In the second step, 12.5% had a low probability of dementia and 20% had a high probability in the same group, while 51.3% had a very low probability of dementia and 21.3% had a very high probability of dementia in the first step of CODEX in uneducated elderly. In the second step in the same group, 12.6% had a low probability and 14.5% had a high probability of dementia. Conclusion: The adapted codex test of Niamey is simple and could be rapidly used to screen dementia among uneducated elderly Muslim prayers, and then could confirm it by complementary cognitive status test validated in the same population. However, it should be confirmed by using a large sample.

友爱的“手”

Sergio was born with a right hand that was not fully formed,but he was used to it and adapted to doing everything with his left hand,including writing.He even man⁃aged to carry his books and water bottle to class,one⁃handed.But being the new kid in school made Sergio very self⁃conscious.

“Adapted Physical Activity”理念在普通高校特殊群体学生体育教育中的阐释

通过对adapted physical activity(APA)理念的本质、概念,实施的条件,发展背景,在特殊群体学生体育教育中的体现及实现,特殊群体学生体育教师的培养体系等方面进行解释和分析,逐步了解和认识到adapted physical activity(APA)理念在特殊群体学生体育教育中作用和价值,以及实现的途径和方法。

Prevalence and dietetic management of mild gastrointestinal disorders in milk-fed infants

AIM: To assess the prevalence of mild gastrointestinal disorders in milk-fed infants in paediatric practice, and to evaluate the effectiveness and satisfaction with dietetic treatment.METHODS: A cross-sectional epidemiological study was first carried out. A total of 285 paediatricians included 3487 children seen during a period of one week. In a second phase an observational, prospective and multicentre study was conducted and 2069 milk-fed infants with mild gastrointestinal disorders (colic, constipation, regurgitation and diarrhoea) were included. There was a baseline visit (start of treatment) and a final visit four weeks later. The effectiveness of the various Novalac formulas, as well as the satisfaction of the parents/tutors and paediatricians with the dietetic treatment were assessed at the final visit.RESULTS: The prevalence of mild gastrointestinal disorders was 27.8% of all paediatrician consultations (9.2%, 7.8%, 6.1% and 4.6% in relation to colic, constipation, regurgitation and diarrhoea, respectively). The several Novalac adapted milk formulas resolved 88.4% of the mild gastrointestinal disorders. Depending on the type of disorder, differences in response rate were observed. The highest effectiveness was recorded with respect to diarrhoea (92.6%), followed by constipation (91.6%), colic (87.6%) and regurgitation (81%). Overall, 91% of the paediatricians and 88.8% of the parents/tutors were satisfied or very satisfied with the Novalac adapted milk formulas.CONCLUSION: Mild gastrointestinal disorders show a high prevalence in paediatric practice. The Novalac adapted milk formulas have been shown to be effective in treating mild gastrointestinal disorders in milk-fed infants in the context of routine clinical practice.

A Finite Difference Scheme on a Priori Adapted Meshes for a Singularly Perturbed Parabolic Convection-Diffusion Equation

A boundary value problem is considered for a singularly perturbed parabolic convection-diffusion equation; we construct a finite difference scheme on α priori （sequentially） adapted meshes and study its convergence. The scheme on α priori adapted meshes is constructed using a majorant function for the singular component of the discrete solution, which allows us to find α priori a subdomain where the computed solution requires a further improvement. This subdomain is defined by the perturbation parameter ε, the step-size of a uniform mesh in χ, and also by the required accuracy of the discrete solution and the prescribed number of refinement iterations K for improving the solution. To solve the discrete problems aimed at the improvement of the solution, we use uniform meshes on the subdomains. The error of the numerical solution depends weakly on the parameter ε. The scheme converges almost ε-uniformly, precisely, under the condition N^-1 = o （ε^v）, where N denotes the number of nodes in the spatial mesh, and the value v = v（K） can be chosen arbitrarily small for suitable K.

The role of γ-aminobutyric acid in aluminum stress tolerance in a woody plant, Liriodendron chinense×tulipifera

The aluminum(Al)cation Al^(3+)in acidic soil shows severe rhizotoxicity that inhibits plant growth and development.Most woody plants adapted to acidic soils have evolved specific strategies against Al^(3+)toxicity,but the underlying mechanism remains elusive.The four-carbon amino acid gamma-aminobutyric acid(GABA)has been well studied in mammals as an inhibitory neurotransmitter;GABA also controls many physiological responses during environmental or biotic stress.The woody plant hybrid Liriodendron(L.chinense×tulipifera)is widely cultivated in China as a horticultural tree and provides high-quality timber;studying its adaptation to high Al stress is important for harnessing its ecological and economic potential.Here,we performed quantitative iTRAQ(isobaric tags for relative and absolute quantification)to study how protein expression is altered in hybrid Liriodendron leaves subjected to Al stress.Hybrid Liriodendron shows differential accumulation of several proteins related to cell wall biosynthesis,sugar and proline metabolism,antioxidant activity,cell autophagy,protein ubiquitination degradation,and anion transport in response to Al damage.We observed that Al stress upregulated glutamate decarboxylase(GAD)and its activity,leading to increased GABA biosynthesis.Additional GABA synergistically increased Al-induced antioxidant enzyme activity to efficiently scavenge ROS,enhanced proline biosynthesis,and upregulated the expression of MATE1/2,which subsequently promoted the efflux of citrate for chelation of Al^(3+).We also showed similar effects of GABA on enhanced Al^(3+)tolerance in Arabidopsis.Thus,our findings suggest a function of GABA signaling in enhancing hybrid Liriodendron tolerance to Al stress through promoting organic acid transport and sustaining the cellular redox and osmotic balance.

Heterosis in locally adapted sorghum genotypes and potential of hybrids for increased productivity in contrasting environments in Ethiopia

Increased productivity in sorghum has been achieved in the developed world using hybrids.Despite their yield advantage,introduced hybrids have not been adopted in Ethiopia due to the lack of adaptive traits,their short plant stature and small grain size.This study was conducted to investigate hybrid performance and the magnitude of heterosis of locally adapted genotypes in addition to introduced hybrids in three contrasting environments in Ethiopia.In total,139 hybrids,derived from introduced seed parents crossed with locally adapted genotypes and introduced R lines,were evaluated.Overall,the hybrids matured earlier than the adapted parents,but had higher grain yield,plant height,grain number and grain weight in all environments.The lowland adapted hybrids displayed a mean better parent heterosis(BPH) of19%,equating to 1160 kg ha-1and a 29% mean increase in grain yield,in addition to increased plant height and grain weight,in comparison to the hybrids derived from the introduced R lines.The mean BPH for grain yield for the highland adapted hybrids was 16% in the highland and 52%in the intermediate environment equating to 698 kg ha-1and 2031 kg ha-1,respectively,in addition to increased grain weight.The magnitude of heterosis observed for each hybrid group was related to the genetic distance between the parental lines.The majority of hybrids also showed superiority over the standard check varieties.In general,hybrids from locally adapted genotypes were superior in grain yield,plant height and grain weight compared to the high parents and introduced hybrids indicating the potential for hybrids to increase productivity while addressing farmers' required traits.

Ecological adaptati ons in fl ue nee the susceptibility of plants in the genus Zantedeschia to soft rot Pectobacterium spp.

Soft rot disease caused by Pectobacterium spp.is responsible for severe agricultural losses in potato,vegetables,and ornamentals.The genus Zantedeschia includes two botanical groups of tuberous ornamental flowers that are highly susceptible to the disease.Previous studies revealed that Z.aethiopica,a member of the section Zantedeschia,is signi ficantly more resistant to Pectobacterium spp.than members of the same genus that belong to the section Aestivae.During early infection,we found different patterns of bacterial colonization on leaves of hosts belonging to the different sections.Similar patterns of bacterial colonization were observed on polydimethylsiloxane(PDMS)arti fi cial inert replicas of leaf surfaces.The replicas con fi rmed the physical effect of leaf texture,in addition to a biochemical plant-bacterium interaction.The differential patterns may be associated with the greater roughness of the abaxial leaf surfaces of Aestivae group that have evolutionarily adapted to mountainous environments,as compared to Zantedeschia group species that have adapted to warm,marshy environments.Transverse leafsections also revealed compact aerenchyma and reduced the total volume of leaf tissue air spaces in Aestivae members.Finally,an analysis ofdefense marker genes revealed differential expression patterns in response to infection,with signi ficantly higher levels of lipoxygenase 2(lox 2)and phenylalanine ammonia lyase(pal)observed in the more resistant Z.aethiopica,suggesting greater activation of induced systemic resistance(ISR)mechanisms in this group.The use of Zantedeschia as a model plant sheds light on how natural ecological adaptations may underlay resistance to bacterial soft rot in cultivated agricultural environments.

KELEA: A Natural Energy That Seemingly Reduces Intermolecular Hydrogen Bonding in Water and Other Liquids

The alternative cellular energy (ACE) pathway was initially identified as a non-immunological defense mechanism against virus infections. It is particularly relevant to the suppression of stealth adapted viruses, which are not normally recognized by the cellular immune system. Many of the methods able to enhance the ACE pathway are consistent with the transfer of a natural energy to the body’s fluids. Additional support for this premise is provided in this paper. The vapor pressure and rate of evaporation of activated water, ethanol and gasoline increase to beyond atmospheric pressure over time. The term KELEA (kinetic energy limiting electrostatic attraction) is proposed for a natural energy that increases the volatility of fluids, seemingly through the loosening of intermolecular hydrogen bonding. KELEA activated fluids have many potential health, agricultural and industrial applications, as well as providing the opportunity for fundamental research.

Multi-Label Chinese Comments Categorization: Comparison of Multi-Label Learning Algorithms

Multi-label text categorization refers to the problem of categorizing text througha multi-label learning algorithm. Text classification for Asian languages such as Chinese isdifferent from work for other languages such as English which use spaces to separate words.Before classifying text, it is necessary to perform a word segmentation operation to converta continuous language into a list of separate words and then convert it into a vector of acertain dimension. Generally, multi-label learning algorithms can be divided into twocategories, problem transformation methods and adapted algorithms. This work will usecustomer's comments about some hotels as a training data set, which contains labels for allaspects of the hotel evaluation, aiming to analyze and compare the performance of variousmulti-label learning algorithms on Chinese text classification. The experiment involves threebasic methods of problem transformation methods: Support Vector Machine, Random Forest,k-Nearest-Neighbor;and one adapted algorithm of Convolutional Neural Network. Theexperimental results show that the Support Vector Machine has better performance.

ON SOLUTIONS OF BACKWARD STOCHASTIC DIFFERENTIAL EQUATIONS WITH JUMPS,WITH UNBOUNDED STOPPING TIMES AS TERMINAL AND WITH NON-LIPSCHITZ COEFFICIENTS,AND PROBABILISTIC INTERPRETATION OF QUASI-LINEAR ELLIPTIC TYPE INTEGRO-DIFFERENTIAL EQUATIO

The existence and uniqueness of solutions to backward stochastic differential equations with jumps and with unbounded stopping time as terminal under the non_Lipschitz condition are obtained. The convergence of solutions and the continuous dependence of solutions on parameters are also derived. Then the probabilistic interpretation of solutions to some kinds of quasi_linear elliptic type integro_differential equations is obtained.

Accurately Predicting the Density and Hydrostatic Compression of Hexahydro-1,3,5-Trinitro-1,3,5-Triazine from First Principles

We predict the densities of crystalline hexahydro-1,3,5-trinitro-1,3,5-triazine(RDX)by introducing a factor of(1+1.5×10^(−4) T)into the wavefunction-based potential of RDX constructed from first principles using the symmetry-adapted perturbation theory and the Williams–Stone–Misquitta method.The predicted values are within an accuracy of 1%of the density from 0 to 430 K and closely reproduced the RDX densities under hydrostatic compression.This work heralds a promising approach to predicting accurately the densities of high explosives at temperatures and pressures to which they are often subjected,which is a long-standing issue in the field of energetic materials.

带边流形上向量场的奇点指标公式及其应用

讨论了M .Morse关于带边流形上向量场的奇点指标公式 ,应用延拓形变成adapted场的方法 ,给出了该公式一个更为简洁本质的证明 ,得到Rn 中单连通区域上连续映射的孤立零点估计 .它可以被看成是辐角原理的一般推广 .

Stealth Adapted Viruses: A Bridge between Molecular Virology and Clinical Psychiatry

Cytopathic “stealth-adapted” viruses bypass the cellular immune defense mechanisms because of molecular deletion or mutation of critical antigen coding genes. They, therefore, do not provoke the inflammatory reaction typical of infections with the conventional viruses from which stealth adapted viruses are derived. Stealth adapted viruses establish persistent, systemic virus infections, which commonly involve the brain. The brain damage can cause major mood and cognitive disorders, fatigue, seizures and various manifestations of an impaired autonomic nervous system. Symptoms can also result from: 1) induced autoimmunity, 2) antibody formation against virus antigens, 3) virus-induced cellular damage to non-brain tissues and 4) induced heightened overall immune reactivity, such that normally unrecognized components of the virus begin to become targeted by the cellular immune system. This last mechanism is relevant to the reported neurological and psychiatric adverse effects of vaccination in certain individuals. It is also appropriate to consider the infectious component of stealth adapted virus infections since family members and others may be at risk for becoming infected.

Nonstationary Wavelets Related to the Walsh Functions

Using the Walsh-Fourier transform, we give a construction of compactly supported nonstationary dyadic wavelets on the positive half-line. The masks of these wavelets are the Walsh polynomials defined by finite sets of parameters. Application to compression of fractal functions are also discussed.