The kinetics of goat sperm is negatively affected after freezing in an extender including zinc oxide nanoparticles.

BACKGROUND: Nanotechnology can benefit livestock industries, especially through postharvest semen manipulation. Zinc oxide nanoparticles (Np-ZnO) are potentially an example. OBJECTIVE: To investigate how the addition of zinc oxide nanoparticles (Np-ZnO) affected the characteristics of post-thawed goat semen. MATERIALS AND METHODS: Seminal pools from four Saanen bucks were used. Semen was diluted in Tris-egg yolk extender, supplemented with Np-ZnO (0, 50, 100 or 200 ug/mL), frozen and stored in liquid nitrogen (-196 degree C), and thawed in a water bath (37 degree C / 30 s). Semen samples were evaluated for sperm kinetics by computer-assisted sperm analysis (CASA), and assessed for other functional properties by epifluorescence microscopy, such as plasma membrane integrity (PMi), acrosomal membrane integrity (ACi) and mitochondrial membrane potential (MMP). RESULTS: For total motility (TM), the group treated with 200 ug/mL Np-ZnO was superior to the control. In straight-line velocity (VSL), the control was better than the group containing 200 ug/mL of Np-ZnO. For average path velocity (VAP), the control was higher than with 100 ug/mL Np-ZnO. For linearity (LIN), the control was higher than with 200 µg/mL Np-ZnO. In straightness (STR), the control and 100 µg/mL Np-ZnO were higher than with 200 ug/mL Np-ZnO. In wobble (WOB), the control was better than the 50 µg/mL Np-ZnO treatment. In PMi, ACi and MMP no significant differences were found. CONCLUSION: The addition of Np-ZnO (200 ug/mL) to the goat semen freezing extender improved the total motility of cells, whilst negatively affecting sperm kinetics. https://doi.org/10.54680/fr24210110512.

Resting-state networks and their relationship with MoCA performance in PD patients.

Although mild cognitive impairment is a common non-motor symptom experienced by individuals with Parkinson's Disease, the changes in intrinsic resting-state networks associated with its onset in Parkinson's remain underexamined. To address the issue, our study sought to examine resting-state network alterations and their association with total performance in the Montreal Cognitive Assessment and its cognitive domains in Parkinson's by means of functional magnetic resonance imaging of 29 Parkinson's patients with normal cognition, 25 Parkinson's patients with mild cognitive impairment, and 13 healthy controls. To contrast the Parkinson's groups with each other and the controls, the images were used to estimate the Z-score coefficient between the regions of interest from the default mode network, the salience network and the central executive network. Our first finding was that default mode and salience network connectivity decreased significantly in Parkinson's patients regardless of their cognitive status. Additionally, default mode network nodes had a negative and salience network nodes a positive correlation with the global assessment in Parkinson's with normal cognition; this inverse relationship of both networks to total score was not found in the group with cognitive impairment. Finally, a positive correlation was found between executive scores and anterior and posterior cortical network connectivity and, in the group with cognitive impairment, between language scores and salience network connectivity. Our results suggest that specific resting-state networks of Parkinson's patients with cognitive impairment differ from those of Parkinson's patients with normal cognition, supporting the evidence that cognitive impairment in Parkinson's Disease displays a differentiated neurodegenerative pattern.

A scoping review on tools and methods for trait prioritization in crop breeding programmes.

Trait prioritization studies have guided research, development and investment decisions for public-sector crop breeding programmes since the 1970s, but the research design, methods and tools underpinning these studies are not well understood. We used PRISMA-ScR (Preferred Reporting Items for Systematic review and Meta-Analysis Protocols) to evaluate research on trait ranking for major crops over the past 40 years (1980-2023). Data extraction and descriptive analysis on 657 papers show uneven attention to crops, lack of systematic sex disaggregation and regional bias. The lack of standardized trait data taxonomy across studies, and inconsistent research design and data collection practices make cross-comparison of findings impossible. In addition, network mapping of authors and donors shows patterns of concentration and the presence of silos within research areas. This study contributes to the next generation of innovation in trait preference studies to produce more inclusive, demand-driven varietal design that moves beyond trait prioritization focused on productivity and yield.

Testing quantum electrodynamics in extreme fields using helium-like uranium.

Quantum electrodynamics (QED), the quantum field theory that describes the interaction between light and matter, is commonly regarded as the best-tested quantum theory in modern physics. However, this claim is mostly based on extremely precise studies performed in the domain of relatively low field strengths and light atoms and ions1-6. In the realm of very strong electromagnetic fields such as in the heaviest highly charged ions (with nuclear charge Z ≫ 1), QED calculations enter a qualitatively different, non-perturbative regime. Yet, the corresponding experimental studies are very challenging, and theoretical predictions are only partially tested. Here we present an experiment sensitive to higher-order QED effects and electron-electron interactions in the high-Z regime. This is achieved by using a multi-reference method based on Doppler-tuned X-ray emission from stored relativistic uranium ions with different charge states. The energy of the 1s1/22p3/2 J = 2 → 1s1/22s1/2 J = 1 intrashell transition in the heaviest two-electron ion (U90+) is obtained with an accuracy of 37 ppm. Furthermore, a comparison of uranium ions with different numbers of bound electrons enables us to disentangle and to test separately the one-electron higher-order QED effects and the bound electron-electron interaction terms without the uncertainty related to the nuclear radius. Moreover, our experimental result can discriminate between several state-of-the-art theoretical approaches and provides an important benchmark for calculations in the strong-field domain.

Golimumab improves health-related quality of life of patients with moderate-to-severe ulcerative colitis: Results of the go-care study.

BACKGROUND: In recent years, improvement of Health-Related Quality of Life (HRQoL) in Ulcerative colitis (UC) has become a relevant measure for treatment efficacy. METHODS: We report results from a multicenter prospective study in Italy investigating HRQoL in adult patients with UC treated with golimumab (GLM). Patients who had shown clinical response after a 6-week induction phase (w0), were followed for an additional 48 weeks (w48) (total 54-week treatment). RESULTS: Of the 159 patients enrolled 90 completed the study. Compared to values at the beginning of treatment (n = 137), significant improvements were observed for mean total Inflammatory Bowel Disease Questionnaire (IBDQ) scores at w0 (168.5) and w48 (181.7). Patients with baseline PMS above the median tended to have greater improvements in IBDQ at w0 (OR 2.037, p = 0.033) and w48 (OR 3.292, p = 0.027). Compared to beginning of GLM treatment, the mean Full Mayo Score (FMS) decreased by 5.9 points at w48, while mean Partial Mayo Score (PMS) decreased by 3.9 points at w0 and by 4.9 points at w48. CONCLUSIONS: GLM improved HRQoL, disease activity and inflammatory biomarkers in UC patients with moderate-to-severely active disease. The greater the burden of disease activity at baseline, the greater the improvement of HRQoL after 24 and 48 weeks of treatment.

Ethoxysclerol injection into the posterior ligament under single puncture arthroscopy for the treatment of recurrent temporomandibular joint dislocation: a novel technique.

The pathogenesis of recurrent chronic dislocation of the temporomandibular joint has been attributed to multiple factors, such as hyperlaxity of the soft tissues or alterations in the size of the temporal eminence. When there are no bone alterations, the injection of sclerosing solutions is an effective treatment that can be performed using a blind technique or with arthroscopy. This study presents an innovative technique for injecting ethoxysclerol into the posterior ligament through single puncture arthroscopy. This approach offers a safe and effective alternative for surgeons without experience in high-complexity arthroscopy who want to ensure precise injection of the agent into the desired anatomical areas.

Aqueous extract OF Moringa oleifera Lam leaves added to freezing extenders damages goat sperm membranes.

BACKGROUND: Semen cryopreservation is a biotechnology used frequently in animal production; however, there are some obstacles, such as those caused by high levels of reactive oxygen species (ROS). Moringa oleifera (MO) is known as a potent source of antioxidants and might be an important adjuvant. OBJECTIVE: The objective of this study was to determine the effect of different concentrations of MO extract supplementation on goat semen cryopreservation efficiency. MATERIALS AND METHODS: Ejaculates (n=6) from four goat breeders were pooled and diluted in skimmed milk (SM) or Tris-egg yolk (TEY)-based extenders and supplemented with different concentrations of MO extract (0, 1, 2 and 5 mg/mL). After the freeze-thaw cycle, sperm kinetics and viability were assessed. RESULTS: With the SM extender, straightness, wobble and plasma membrane integrity were lower than in the control group (P < 0.05). With the TEY extender, wobble was lower in with 5 mg/mL MO extract than in the control group (P < 0.05). As regards sperm ultrastructure, evaluated by SEM, the MO extract, regardless of the diluent used, damaged the membrane of sperm cells in a dose-dependent manner. CONCLUSION: The addition of aqueous extract of MO leaves in both diluents at all concentrations tested affects the parameters of sperm progressivity and damages the plasma membrane in a dose-dependent manner. DOI: 10.54680/fr23310110712.

CFAP45, a heterotaxy and congenital heart disease gene, affects cilia stability.

Congenital heart disease (CHD) is the most common and lethal birth defect, affecting 1.3 million individuals worldwide. During early embryogenesis, errors in Left-Right (LR) patterning called Heterotaxy (Htx) can lead to severe CHD. Many of the genetic underpinnings of Htx/CHD remain unknown. In analyzing a family with Htx/CHD using whole-exome sequencing, we identified a homozygous recessive missense mutation in CFAP45 in two affected siblings. CFAP45 belongs to the coiled-coil domain-containing protein family, and its role in development is emerging. When we depleted Cfap45 in frog embryos, we detected abnormalities in cardiac looping and global markers of LR patterning, recapitulating the patient's heterotaxy phenotype. In vertebrates, laterality is broken at the Left-Right Organizer (LRO) by motile monocilia that generate leftward fluid flow. When we analyzed the LRO in embryos depleted of Cfap45, we discovered "bulges" within the cilia of these monociliated cells. In addition, epidermal multiciliated cells lost cilia with Cfap45 depletion. Via live confocal imaging, we found that Cfap45 localizes in a punctate but static position within the ciliary axoneme, and depletion leads to loss of cilia stability and eventual detachment from the cell's apical surface. This work demonstrates that in Xenopus, Cfap45 is required to sustain cilia stability in multiciliated and monociliated cells, providing a plausible mechanism for its role in heterotaxy and congenital heart disease.

Prevalence of depression and anxiety in older people in low- and middle- income countries in Africa, Asia and South America: A systematic review and meta-analysis.

BACKGROUND: There is rapid growth of older people in Low- and Middle- Income Countries (LMICs). The aim of this review was to assess the literature on prevalence of anxiety and depression in this demographic, which to our knowledge, has not yet been conducted. METHODS: Databases including Medline, PsychInfo, Embase, Scielo and African Journals Online were searched for terms including "mental disorders", "neurotic disorders", "mood disorders" and "anxiety disorders". Studies published between 1990 and 2020 providing data on older people (≥50 years) in LMICs (defined by World Bank Criteria) were included and quality-assessed. Meta-analysis was conducted on a subset of higher-quality studies to derive pooled prevalence estimates of depression. RESULTS: One hundred and forty relevant studies were identified, of which thirty-two were included in meta-analysis. One hundred and fifteen studies reported depression prevalence only, 19 reported both depression and anxiety, and six reported anxiety only. In all studies identified, depression prevalence ranged from 0.5 % to 62.7 %, and Generalised Anxiety Disorder prevalence ranged from 0.2 % to 32.2 %. The pooled prevalence of depression on meta-analysis was 10.5 % (95 % CI, 8.9 % - 11.2 %). Reported prevalence rates of depression were significantly different in studies using ICD-10 compared with DSM criteria, and between community and clinical settings. LIMITATIONS: The search strategy contained bias towards English language papers and high income country (HIC) publications. There is significant heterogeneity within the meta-analysis. DISCUSSION: A wide range of methodologies and clinical criteria are used in prevalence studies of depression and anxiety in older people. Studies using screening tools found higher prevalence rates; clinicians and researchers should ensure diagnosis is made with gold-standard clinical criteria. Meta-analysis data suggest that rates of depression are similar in older people in LMICs compared to HICs but mental healthcare resources are limited, suggesting a large potential treatment gap.

Addressing high cervical cancer rates in the Rio Grande Valley along the Texas-Mexico border: a community-based initiative focused on education, patient navigation, and medical provider training/telementoring.

AIMS: Cervical cancer incidence and mortality rates are approximately 55% higher in the Rio Grande Valley (RGV) along the Texas-Mexico border compared with the average rates in the US. Our aim was to improve cervical cancer prevention efforts in the RGV through a comprehensive multilevel intervention initiative focused on community education, patient navigation, and training of local providers. METHODS: We initiated a program in the RGV which consisted of (1) community education, (2) patient navigation, and (3) a training/mentoring program for local medical providers including hands-on training courses coupled with telementoring using Project ECHO® (Extension for Community Health Outcomes). We assessed the number of women undergoing cervical cancer screening, diagnosis, and treatment at three participating clinics caring for underserved women in the region. RESULTS: From November 2014 to October 2018, 14,846 women underwent cervical cancer screening. A total of 2030 (13.7%) women underwent colposcopy for abnormal results (179% increase over baseline) and 453 women underwent loop electrosurgical excision procedures (LEEPs) for treatment of cervical dysplasia. Invasive cancer was diagnosed in 39 women who were navigated to a gynecologic oncologist for treatment. Seven local medical providers were trained to perform colposcopy and/or LEEP. Project ECHO telementoring videoconferences were held every 2 weeks for a total 101 sessions with an average of 22 participants per session and a total of 180 patient cases presented and discussed. CONCLUSIONS: Our program led to a large number of women undergoing diagnosis and treatment of cervical dysplasia in the RGV. If sustained, we anticipate these efforts will decrease cervical cancer rates in the region. The program is currently being expanded to additional underserved areas of Texas and globally to low- and middle-income countries.

Reverse engineering in forensic investigations: a new approach to bite mark analysis.

The study of bite marks provides crucial elements that contribute towards identifying the biter. In many cases, it assumes importance when bite marks are detected on the body of a victim of violence, but it could also be relevant when the bite marks are seen on food substances at the crime scene. In both circumstances, comparing the bite marks with a suspect's dentition can be decisive in confirming or excluding the culpability. In this case report, a bun (bread roll) with the sign of a bite was found at the crime scene. We report a pilot study using 3D reproduction of the bite mark on the bun and dental models of the alleged biter and the victim. A reverse engineering process was used to obtain digital 3D models of the bitten bun and the dental models by taking numerous photographs and stitching them together using a software called Metashape by Agisoft. The last step was to compare the bitemark to the two dental models, evaluating the spatial distance, the degree of overlap, and the degree of interpenetration. The results confirmed the usefulness of reverse engineering in forensic investigations showing the compatibility between the victim's teeth and the bite mark on the bun.

Terapia en espejo y de observación de la acción en niños con parálisis cerebral espástica unilateral: estudio de viabilidad / Mirror and action observation therapy in children with unilateral spastic cerebral palsy: a feasibility study

Introducción: La parálisis cerebral espástica unilateral afecta a la función de la extremidad superior. Las terapias en espejo y de observación de la acción domiciliaria pueden ser útiles en su tratamiento. El objetivo ha sido evaluar la viabilidad de programas de terapia de observación de la acción y terapia en espejo combinada con observación de la acción domiciliaria en niños con parálisis cerebral espástica unilateral. Sujetos y métodos: El estudio de viabilidad incluyó a niños (6-12 años), asignados aleatoriamente a dos grupos: terapia de observación de la acción y terapia en espejo y observación de la acción. Se realizaron 20 sesiones domiciliarias de una hora, y se incluyeron actividades unimanuales y bimanuales. Se evaluó la viabilidad de las intervenciones y procedimientos, y el uso espontáneo (escala Assisting Hand Assessment) y la funcionalidad (Jebsen Taylor Hand Function Test) de la extremidad superior. Resultados: Se reclutaron 25 familias, y 17 cumplieron los criterios de inclusión. Doce niños (8,75 ± 2,38 años) participaron en el estudio. Todas las familias completaron las intervenciones y no existieron efectos adversos. La dosis total de intervención fue superior al 96%. Tras la intervención, se hallaron cambios clínicamente relevantes en ambos grupos en el uso espontáneo de la extremidad superior, así como en la funcionalidad en el grupo de terapia de observación de la acción. Conclusiones: La terapia de observación de la acción y la terapia en espejo combinada con terapia de observación de la acción se consideran viables para aplicarse en el hogar y dirigidas a niños con parálisis cerebral espástica unilateral.(AU)

Introduction: Unilateral spastic cerebral palsy affects upper extremity function. Mirror and home-based action observation therapies may be useful in its treatment. The aim has been to evaluate the feasibility of action observation therapy and mirror therapy programmes combined with home action observation in children with unilateral spastic cerebral palsy. Subjects and methods: The feasibility study included children (6-12 years old), randomly assigned to two groups: action observation therapy and mirror therapy and action observation. Twenty-hour home sessions were conducted, including unimanual and bimanual activities. Feasibility of interventions and procedures, and spontaneous use (Assisting Hand Assessment scale) and functionality (Jebsen Taylor Hand Function Test) of the upper extremity were assessed. Results: Twenty-five families were recruited, with 17 meeting the inclusion criteria. Twelve children (8.75 ± 2.38 years) participated in the study. All families completed the interventions, with no adverse effects. The total intervention dose was above 96%. After the intervention, clinically relevant changes were found in both groups in spontaneous use of the upper extremity, as well as in functionality in the action observation therapy group. Conclusions: Action observation therapy and mirror therapy combined with action observation therapy are considered feasible to be applied at home and aimed at children with unilateral spastic cerebral palsy.(AU)

[Mirror and action observation therapy in children with unilateral spastic cerebral palsy: a feasibility study]. / Terapia en espejo y de observación de la acción en niños con parálisis cerebral espástica unilateral: estudio de viabilidad.

INTRODUCTION: Unilateral spastic cerebral palsy affects upper extremity function. Mirror and home-based action observation therapies may be useful in its treatment. The aim has been to evaluate the feasibility of action observation therapy and mirror therapy programmes combined with home action observation in children with unilateral spastic cerebral palsy. SUBJECTS AND METHODS: The feasibility study included children (6-12 years old), randomly assigned to two groups: action observation therapy and mirror therapy and action observation. Twenty-hour home sessions were conducted, including unimanual and bimanual activities. Feasibility of interventions and procedures, and spontaneous use (Assisting Hand Assessment scale) and functionality (Jebsen Taylor Hand Function Test) of the upper extremity were assessed. RESULTS: Twenty-five families were recruited, with 17 meeting the inclusion criteria. Twelve children (8.75 ± 2.38 years) participated in the study. All families completed the interventions, with no adverse effects. The total intervention dose was above 96%. After the intervention, clinically relevant changes were found in both groups in spontaneous use of the upper extremity, as well as in functionality in the action observation therapy group. CONCLUSIONS: Action observation therapy and mirror therapy combined with action observation therapy are considered feasible to be applied at home and aimed at children with unilateral spastic cerebral palsy.

TITLE: Terapia en espejo y de observación de la acción en niños con parálisis cerebral espástica unilateral: estudio de viabilidad.Introducción. La parálisis cerebral espástica unilateral afecta a la función de la extremidad superior. Las terapias en espejo y de observación de la acción domiciliaria pueden ser útiles en su tratamiento. El objetivo ha sido evaluar la viabilidad de programas de terapia de observación de la acción y terapia en espejo combinada con observación de la acción domiciliaria en niños con parálisis cerebral espástica unilateral. Sujetos y métodos. El estudio de viabilidad incluyó a niños (6-12 años), asignados aleatoriamente a dos grupos: terapia de observación de la acción y terapia en espejo y observación de la acción. Se realizaron 20 sesiones domiciliarias de una hora, y se incluyeron actividades unimanuales y bimanuales. Se evaluó la viabilidad de las intervenciones y procedimientos, y el uso espontáneo (escala Assisting Hand Assessment) y la funcionalidad (Jebsen Taylor Hand Function Test) de la extremidad superior. Resultados. Se reclutaron 25 familias, y 17 cumplieron los criterios de inclusión. Doce niños (8,75 ± 2,38 años) participaron en el estudio. Todas las familias completaron las intervenciones y no existieron efectos adversos. La dosis total de intervención fue superior al 96%. Tras la intervención, se hallaron cambios clínicamente relevantes en ambos grupos en el uso espontáneo de la extremidad superior, así como en la funcionalidad en el grupo de terapia de observación de la acción. Conclusiones. La terapia de observación de la acción y la terapia en espejo combinada con terapia de observación de la acción se consideran viables para aplicarse en el hogar y dirigidas a niños con parálisis cerebral espástica unilateral.

Membrane potential drives the exit from pluripotency and cell fate commitment via calcium and mTOR.

Transitioning from pluripotency to differentiated cell fates is fundamental to both embryonic development and adult tissue homeostasis. Improving our understanding of this transition would facilitate our ability to manipulate pluripotent cells into tissues for therapeutic use. Here, we show that membrane voltage (Vm) regulates the exit from pluripotency and the onset of germ layer differentiation in the embryo, a process that affects both gastrulation and left-right patterning. By examining candidate genes of congenital heart disease and heterotaxy, we identify KCNH6, a member of the ether-a-go-go class of potassium channels that hyperpolarizes the Vm and thus limits the activation of voltage gated calcium channels, lowering intracellular calcium. In pluripotent embryonic cells, depletion of kcnh6 leads to membrane depolarization, elevation of intracellular calcium levels, and the maintenance of a pluripotent state at the expense of differentiation into ectodermal and myogenic lineages. Using high-resolution temporal transcriptome analysis, we identify the gene regulatory networks downstream of membrane depolarization and calcium signaling and discover that inhibition of the mTOR pathway transitions the pluripotent cell to a differentiated fate. By manipulating Vm using a suite of tools, we establish a bioelectric pathway that regulates pluripotency in vertebrates, including human embryonic stem cells.

Evaluation of factors associated with trust in telemedicine in patients with inflammatory bowel disease during COVID-19 pandemic: a multicenter cross-sectional survey.

OBJECTIVE: Telemedicine (TM) has had a powerful impact in recent years, particularly on managing chronic diseases such as inflammatory bowel disease (IBD). Knowing patients' expectations and concerns is essential to increase their confidence in this mode of medical care. PATIENTS AND METHODS: We interviewed a large cohort of IBD patients enrolled at two Italian tertiary referral centers to investigate their trust in TM. RESULTS: A total of 376 patients completed the survey and were included in the study: 293 (77.9%) considered TM valuable for managing their disease, and 307 (85%) wanted to have TM service at their center. However, only 99 patients (26.3%) believed that TM guarantees the same level of care as the in-person visit. Among the socio-demographic variables, those independently associated with trust in TM were the higher education qualification (p=0.02) and the level of competence in information and communication technologies (ICT) (p=0.03). CONCLUSIONS: Our findings highlighted the importance of equipping IBD patients with basic ICT skills to utilize TM services and increase their confidence in ICT with the help of caregivers. Additionally, to improve the perceived value of TM, it will be helpful to use additional tools such as telemonitoring of disease activity using patients' reported outcomes or remote measurement of fecal calprotectin.

Temporomandibular joint arthroscopy in advanced stages of internal derangement: a retrospective cohort study on the influence of age.

The aim of this investigation was to evaluate the outcomes of patients with advanced internal derangement of the temporomandibular joint who underwent operative arthroscopy, according to age stratified into two groups: <45 years and ≥45 years. The study included a series of 194 patients. Outcome variables were pain intensity and mandibular mobility. Additionally, the difference in arthroscopic findings in these age groups was studied. The data analysis included the paired t-test, χ2 test, and two-way analysis of variance, with a P-value <0.05 indicating statistical significance. A significant reduction in pain and an improvement in maximum inter-incisal opening (MIO) was observed in both groups starting at 1 month of follow-up (P < 0.01). However, the results for MIO were worse in the ≥45 years group (P=0.036) at 12- and 18-months follow-up. Regarding arthroscopic findings, the study showed a higher prevalence of severe chondromalacia in the ≥45 years group (P = 0.031) and disc displacement without reduction in the <45 years group (P = 0.020). Analysis of variance showed a greater pain reduction if no obliteration of the articular space was observed (P = 0.039). In young and older patients, operative arthroscopy can be useful for short-term treatment in advanced stages of internal derangement of the temporomandibular joint.

Nodal is a short-range morphogen with activity that spreads through a relay mechanism in human gastruloids.

Morphogens are signaling molecules that convey positional information and dictate cell fates during development. Although ectopic expression in model organisms suggests that morphogen gradients form through diffusion, little is known about how morphogen gradients are created and interpreted during mammalian embryogenesis due to the combined difficulties of measuring endogenous morphogen levels and observing development in utero. Here we take advantage of a human gastruloid model to visualize endogenous Nodal protein in living cells, during specification of germ layers. We show that Nodal is extremely short range so that Nodal protein is limited to the immediate neighborhood of source cells. Nodal activity spreads through a relay mechanism in which Nodal production induces neighboring cells to transcribe Nodal. We further show that the Nodal inhibitor Lefty, while biochemically capable of long-range diffusion, also acts locally to control the timing of Nodal spread and therefore of mesoderm differentiation during patterning. Our study establishes a paradigm for tissue patterning by an activator-inhibitor pair.