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Background and objective: While programmes such as the European Basic Laparoscopic Urological Skills have made strides in foundational training, a significant gap exists for intermediate and advanced laparoscopy education. Our objective is to develop and validate the European laparoscopic intermediate urological skills (LUSs2) curriculum, which will establish uniformity in the training of urological laparoscopic procedures and facilitate proficiency among practitioners. Methods: The study combines a literature review, cognitive task analysis development by a steering group, and a two-round Delphi survey involving international experts in urological laparoscopy. Consensus was defined as agreement of ≥70% among experts. The survey included statements on various laparoscopic procedures, assessed on a Likert scale from 1 (strongly disagree) to 9 (strongly agree). Key findings and limitations: The Delphi process achieved consensus on 85% (235/275) of statements, indicating a strong agreement on the curriculum’s content. Areas covered include renal hilum dissection, major vessel injury management, enucleation and renorrhaphy, vesicourethral anastomosis, and pyeloplasty. Limitations include the nonsystematic nature of the literature review and potential biases inherent in expert-based consensus methods. Conclusions and clinical implications: The LUSs2 curriculum significantly advances the standardised training of laparoscopic urological skills. It offers a detailed, consensus-validated framework that addresses the need for uniformity in surgical education and aims to enhance surgical proficiency and patient care. Patient summary: This study presents the development of a new standardised training curriculum for urological laparoscopic surgery. We intend this curriculum to improve the quality of surgical training and ensure high-quality patient care.

Background and objective: The tumor microenvironment (TME) in non–muscle-invasive bladder cancer (NMIBC) plays an important role in the anticancer response. We aimed to identify the prognostic biomarkers in the TME of patients with NMIBC for progression to ≥T2. Methods: From our institutional database, 40 patients with T1 high-risk NMIBC who progressed were pair matched for Club Urologico Español de Tratamiento Oncologico (CUETO) progression variables with 80 patients who never progressed despite longer follow-up. Progression was defined as ≥T2 or extravesical disease. Patients were treated at least with bacillus Calmette-Guérin (BCG) induction (five or more of six doses). Immunohistochemical (IHC) markers for the TME were used on tissue at first T1 diagnosis: CD8-PanCK, GZMB-CD8-FOXP3, CD163, PD-L1 SP142/SP263, fibroblast activation protein-α (FAP), and CK5-GATA3. Full tissue slides were annotated digitally. Relative marker area (IHC-positive area/total area) or density (IHC-positive cells per area; n/mm2) was calculated, differentiating between regions of interest (ROIs; T1, Ta, and carcinoma in situ) and between compartments (stromal, epithelial, and combined). Differences in IHC variables were assessed using the t test, for continuous variables using analysis of variance and comparisons of more than two groups using Tukey’s test. Conditional logistic regression for progression at 5-yr follow-up was performed with clusters based on pair matching. Key findings and limitations: Only FAP expression (increase per 50%) in T1 (odds ratio [OR]: 1.33; 95% confidence interval [CI]: 1.04–1.70) and all ROIs combined (OR: 1.62; 95% CI: 1.14–2.29) correlated significantly with progression. None of the other clinicopathological/IHC variables correlated with progression. Conclusions and clinical implications: FAP is a potential prognostic biomarker for progression in high-risk NMIBC. FAP is a marker for cancer-associated fibroblasts and is linked to immunosuppression and neoangiogenesis, which makes future investigation clinically relevant. Patient summary: We found that progression of high-risk non–muscle-invasive bladder cancer to muscle-invasive disease is less in patients with lower fibroblast activation protein-α (FAP) expression, which is a marker for cancer-associated fibroblasts.

Abstract The nuclear matrix is a nuclear compartment that has diverse functions in chromatin regulation and transcription. However, how this structure influences epigenetic modifications and gene expression in plants is largely unknown. In this study, we show that a nuclear matrix binding protein, AHL22, together with the two transcriptional repressors FRS7 and FRS12, regulates hypocotyl elongation by suppressing the expression of a group of genes known as SMALL AUXIN UP RNAs (SAURs) in Arabidopsis thaliana. The transcriptional repression of SAURs depends on their attachment to the nuclear matrix. The AHL22 complex not only brings these SAURs, which contain matrix attachment regions (MARs), to the nuclear matrix, but it also recruits the histone deacetylase HDA15 to the SAUR loci. This leads to the removal of H3 acetylation at the SAUR loci and the suppression of hypocotyl elongation. Taken together, our results indicate that MAR-binding proteins act as a hub for chromatin and epigenetic regulators. Moreover, we present a mechanism by which nuclear matrix attachment to chromatin regulates histone modifications, transcription, and hypocotyl elongation.

Combined oral contraceptives, comprising of both an oestrogen and a progestin component, are released in aquatic environments and potentially pose a risk to aquatic wildlife by their capacity to disrupt physiological mechanisms.In this study, the endocrine disruptive potential of two mixtures, 17α-ethinylestradiol (EE2), a synthetic oestrogen, or estetrol (E4), a natural oestrogen, with the progestin drospirenone (DRSP) have been characterised in three generations of zebrafish, according to an adapted Medaka Extended One Generation Reproduction Test. Zebrafish (Danio rerio) were exposed to a range of concentrations of EE2/DRSP and E4/DRSP (∼1×, ∼3×, ∼10× and ∼30× predicted environmental concentration, PEC). Survival, growth, hatching success, fecundity, fertilisation success, vitellogenin (VTG), gonad histopathology, sex differentiation, and transcriptional analysis of genes related to gonadal sex steroid hormones synthesis were assessed.In the F0 generation, exposure to EE2/DRSP at ∼10 and ∼30× PEC decreased fecundity and increased male VTG concentrations. The highest concentration of EE2/DRSP also affected VTG concentrations in female zebrafish and the expression of genes implicated in steroid hormones synthesis. In the F1 generation, sex determination was impaired in fish exposed to EE2/DRSP at concentrations as low as ∼3× PEC. Decreased fecundity and fertility, and abnormal gonadal histopathology were also observed. No effects were observed in the F2 generation. In contrast, E4/DRSP induced only minor histopathological changes and an increase in the proportion of males, at the highest concentration tested (∼30× PEC) in the F1 generation and had no effect on hatching success of F2 generation.Overall, this study suggests that the combination E4/DRSP has a more favourable environmental profile than EE2/DRSP.

Introduction Hysterectomy is one of the most common surgeries performed in women. Minimally invasive methods are on the rise globally as they have been shown to decrease surgical morbidity compared with abdominal hysterectomy. Hysterectomy by vaginal natural orifice transluminal endoscopic surgery (vNOTES) is the latest innovation. It combines the vaginal approach and endoscopy via the vagina. Large pragmatic randomised controlled trials (RCTs) are lacking comparing outcomes after vNOTES, vaginal hysterectomy (VH) and laparoscopic hysterectomy (LH).Methods Multicentre pragmatic RCT aiming to recruit 1000 women aged 18–75 years undergoing hysterectomy for benign disease. The RCT includes two identical substudies (groups A and B). If VH is considered safe and feasible, the patient will be randomised within group A (VH vs vNOTES). If VH is not considered safe or feasible, patients will be randomised within group B (LH vs vNOTES).Analysis Primary outcome is the proportion of women leaving the hospital within 12 hours after surgery. Secondary outcomes are hospitalisation time, conversion rates, duration of the surgical procedure, intraoperative complications, postoperative complications and readmission.Ethics and dissemination The Ethical Board Committee at Imelda Hospital, Bonheiden, Belgium, has approved the research protocol 230704 (principal investigator). Before including patients, all centres will require local or national ethical approval. The results of the study will be published in international peer-reviewed journals.Trial registration number NCT05971875.

Abstract Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most common genetic cause of Parkinson’s disease (PD), with growing importance also for Crohn’s disease and cancer. LRRK2 is a large and complex protein possessing both GTPase and kinase activity. Moreover, LRRK2 activity and function can be influenced by its phosphorylation status. In this regard, many LRRK2 PD-associated mutants display decreased phosphorylation of the constitutive phosphorylation cluster S910/S935/S955/S973, but the role of these changes in phosphorylation status with respect to LRRK2 physiological functions remains unknown. Here, we propose that the S910/S935/S955/S973 phosphorylation sites act as key regulators of LRRK2-mediated autophagy under both basal and starvation conditions. We show that quadruple LRRK2 phosphomutant cells (4xSA; S910A/S935A/S955A/S973A) have impaired lysosomal functionality and fail to induce and proceed with autophagy during starvation. In contrast, treatment with the specific LRRK2 kinase inhibitors MLi-2 (100 nM) or PF-06447475 (150 nM), which also led to decreased LRRK2 phosphorylation of S910/S935/S955/S973, did not affect autophagy. In explanation, we demonstrate that the autophagy impairment due to the 4xSA LRRK2 phospho-dead mutant is driven by its enhanced LRRK2 kinase activity. We show mechanistically that this involves increased phosphorylation of LRRK2 downstream targets Rab8a and Rab10, as the autophagy impairment in 4xSA LRRK2 cells is counteracted by expression of phosphorylation-deficient mutants T72A Rab8a and T73A Rab10. Similarly, reduced autophagy and decreased LRRK2 phosphorylation at the constitutive sites were observed in cells expressing the pathological R1441C LRRK2 PD mutant, which also displays increased kinase activity. These data underscore the relation between LRRK2 phosphorylation at its constitutive sites and the importance of increased LRRK2 kinase activity in autophagy regulation and PD pathology.

Simple Summary: Bladder cancer is the ninth most commonly diagnosed form of cancer in both sexes worldwide and the fifth in Europe. The most common form, non-muscle-invasive bladder cancer, is highly prevalent with high recurrence rates and has wide range of outcomes that is partially due to the variability in the treatment delivered. Therefore, some recommendations have been done by the European Association of Urology to standardize their management. Several quality control indicators have been proposed to monitor the adherence of urologists and hospitals to these recommendations. A quality control indicator program has been initiated in the hospitals that are a part of the Flemish Hospital Network in June 2013 using a specific prospective registry. We have recently published the first analysis of these quality control indicators, which showed significant differences between the hospitals. Before publishing the second analysis with more patients and additional quality control indicators, we aimed to describe the characteristics of the cohort in this study. Purpose: Bladder cancer (BC) is a heterogeneous disease with varying outcomes, influenced by disease heterogeneity and variability in treatment and follow-up. Risk groups have been established for non–muscle-invasive BC (NMIBC) to standardize therapy, and several quality control indicators (QCIs) monitor adherence to these risk group-based guidelines. However, controversial results had been obtained regarding the oncological benefits of these QCIs until recent high-quality studies from large registries showed their usefulness. To improve adherence to the European Association of Urology (EAU) Guidelines and benchmark current care in Flemish hospitals within Vlaams Ziekenhuisnetwerk–KU Leuven (VZNKUL), a QCI program for NMIBC was initiated in 2013. This study aims to describe the demographic, clinical, and treatment data of patients enrolled in this program. Participants: The VZNKUL–NMIBC Quality Indicators Program Registry is a prospective cohort including patients treated and followed up with at seven academic and non-academic Flemish hospitals since June 2013. Data collection includes patient characteristics, tumor data, treatment, and oncological outcomes. Findings to date: From June 2013 to December 2020, 4744 transurethral resections of bladder tumors (TURBTs) from 2237 unique patients were analyzed. Most patients (80%) were men with a median age of 73. The median time from diagnosis to TURBT was 19 days. A single tumor was detected in 37% of TURBTs. Tumors larger than 3 cm were found in 20.8% of cases. In 46% of TURBTs, a reTURBT was scheduled according to guidelines. The complication rates were 7.5% and 2.4% for bladder perforation and bleeding, respectively. Postoperative single intravesical instillation of chemotherapy (SIVIC) was administered to 56.9% of 1533 indicated patients with a median time to administration of 4.7 h. Among the cohort, 60.4% had NMIBC, and 9.3% had muscle-invasive BC. Of 972 high-risk patients, 60.7% received adequate BCG induction, while 39.4% received adequate maintenance. After BCG induction ± maintenance, 39.7% were tumor-free, with 17.7% recurrence and 4% progression to muscle-invasive BC. BCG treatment was terminated early for 17% of patients due to intolerance. Early cystectomy was performed for 2.4% of the BCG-naïve patients, and 27.7% of patients with BCG failure underwent a BCG rechallenge. For intermediate-risk patients, 2.1% received adequate BCG, and 23% received intravesical chemotherapy. The median follow-up was 57 months. Five-year recurrence-free, progression-free, cancer-free, overall, and cancer-specific survival rates were 53%, 91.6%, 89%, 70.6%, and 95.6%, respectively, for the NMIBC patients. Of 400 non-metastatic MIBC patients, 217 (54.3%) underwent radical cystectomy (RC), of whom 46% received neoadjuvant chemotherapy, while 18 (4.5%) refused RC, and 74 (18.5%) were considered unfit for the surgery. Future plans: The VZNKUL–NMIBC Quality Indicators Program Registry will continue collecting data to evaluate QCIs and monitor treatment quality, enabling hospitals to benchmark their performance and improve patient care. Additionally, the registry's real-world data can support research and international collaboration. Trial registration: The study was registered on ClinicalTrials.gov (NCT04167332). [ABSTRACT FROM AUTHOR]

Aggregation of the protein α-Synuclein (αSyn) is a hallmark of Parkinson’s disease (PD), dementia with Lewy bodies (DLB) and multiple systems atrophy, and alleviating the extent of αSyn pathology is an attractive strategy against neurodegeneration. The engineered binding protein β-wrapin AS69 binds monomeric αSyn. AS69 reduces primary and secondary nucleation as well as fibril elongation in vitro. It also mitigates aSyn pathology in a mouse model based on intrastriatal injection of aSyn pre-formed fibrils (PFFs). Since the PFF-based model does not represent all aspects of PD, we tested here whether AS69 can reduce neurodegeneration resulting from αSyn overexpression. Human A53T-αSyn was overexpressed in the mouse Substantia nigra (SN) by using recombinant adeno-associated viral vector (rAAV). AS69 was also expressed by rAAV transduction. Behavioral tests and immunofluorescence staining were used as outcomes. Transduction with rAAV-αSyn resulted in αSyn pathology as reported by phospho-αSyn staining and caused degeneration of dopaminergic neurons in the SN. The co-expression of rAAV-AS69 did not reduce αSyn pathology or the degeneration of dopaminergic neurons. We conclude that αSyn monomer binding by rAAV-AS69 was insufficient to protect from aSyn pathology resulting from αSyn overexpression.

The increase in practices related to enhancing penile size can be attributed to the belief that an improved genital appearance contributes to a man’s virility, coupled with an altered self-perception of his body. It is crucial to tailor interventions to meet the genuine needs of patients by thoroughly assessing their history, psychological state, and potential surgical benefits, all while considering the associated risks of complications. This systematic review aims to summarize the available evidence on outcomes, complications, and quality of life after penile augmentation surgery, examining both minimally invasive and more radical techniques. A search of the PubMed and Scopus databases, focusing on English-language papers published in the last 15 years, was performed in December 2023. Papers discussing surgery in animal models and case reports were excluded from the present study unless further evaluated in a follow-up case series. The primary outcomes were changes in penile dimensions, specifically in terms of length and girth, as well as the incidence of surgical complications and the impact on quality of life. A total of 1670 articles were retrieved from the search and 46 were included for analysis. Procedures for penile length perceived enhancements include lipoplasty, skin reconstruction plasty, V-Y and Z plasty, flap reconstruction, scrotoplasty, ventral phalloplasty, and suspensory ligament release; techniques for increasing corporal penile length include penile disassembly, total phalloplasty, and sliding elongation. Finally, penile girth enhancement may be performed using soft tissue fillers, grafting procedures, biodegradable scaffolds, and Penuma®. In conclusion, while penile augmentation surgeries offer potential solutions for individuals concerned about genital size, the risks and complexities need to be accounted for.

Abstract In Parkinson’s disease (PD) misfolded alpha-synuclein (aSyn) accumulates in the substantia nigra, where dopaminergic neurons are progressively lost. The mechanisms underlying aSyn pathology are still unclear, but they are hypothesized to involve the autophagy-lysosome pathway (ALP). LRRK2 mutations are a major cause of familial and sporadic PD, and LRRK2 kinase activity has been shown to be involved in pS129-aSyn inclusion modulation. We observed selective downregulation of the novel PD risk factor RIT2 in vitro and in vivo. Rit2 overexpression in G2019S-LRRK2 cells rescued ALP abnormalities and diminished aSyn inclusions. In vivo, viral mediated overexpression of Rit2 operated neuroprotection against AAV-A53T-aSyn. Furthermore, Rit2 overexpression prevented the A53T-aSyn-dependent increase of LRRK2 kinase activity in vivo. On the other hand, reduction of Rit2 levels leads to defects in the ALP, similar to those induced by the G2019S-LRRK2 mutation. Our data indicate that Rit2 is required for correct lysosome function, inhibits overactive LRRK2 to ameliorate ALP impairment, and counteracts aSyn aggregation and related deficits. Targeting Rit2 could represent an effective strategy to combat neuropathology in familial and idiopathic PD.

Prostate cancer (PCa) is the most common cancer in men worldwide. Despite better and more intensive treatment options in earlier disease stages, a large subset of patients still progress to metastatic castration-resistant PCa (mCRPC). Recently, poly-(ADP-ribose)-polymerase (PARP)-inhibitors have been introduced in this setting. The TALAPRO-2 and PROpel trials both showed a marked benefit of PARPi in combination with an androgen receptor signaling inhibitor (ARSI), compared with an ARSI alone in both the homologous recombination repair (HRR)-mutated, as well as in the HRR-non-mutated subgroup. In this review, we present a comprehensive overview of how maximal AR-blockade via an ARSI in combination with a PARPi has a synergistic effect at the molecular level, leading to synthetic lethality in both HRR-mutated and HRR-non-mutated PCa patients. PARP2 is known to be a cofactor of the AR complex, needed for decompacting the chromatin and start of transcription of AR target genes (including HRR genes). The inhibition of PARP thus reinforces the effect of an ARSI. The deep androgen deprivation caused by combining androgen deprivation therapy (ADT) with an ARSI, induces an HRR-like deficient state, often referred to as “BRCA-ness”. Further, PARPi will prevent the repair of single-strand DNA breaks, leading to the accumulation of DNA double-strand breaks (DSBs). Due to the induced HRR-deficient state, DSBs cannot be repaired, leading to apoptosis.

Abstract To meet the increasing global demand for food, feed, fibre and other plant‐derived products, a steep increase in crop productivity is a scientifically and technically challenging imperative. The CropBooster‐P project, a response to the H2020 call ‘Future proofing our plants’, is developing a roadmap for plant research to improve crops critical for the future of European agriculture by increasing crop yield, nutritional quality, value for non‐food applications and sustainability. However, if we want to efficiently improve crop production in Europe and prioritize methods for crop trait improvement in the coming years, we need to take into account future socio‐economic, technological and global developments, including numerous policy and socio‐economic challenges and constraints. Based on a wide range of possible global trends and key uncertainties, we developed four extreme future learning scenarios that depict complementary future developments. Here, we elaborate on how the scenarios could inform and direct future plant research, and we aim to highlight the crop improvement approaches that could be the most promising or appropriate within each of these four future world scenarios. Moreover, we discuss some key plant technology options that would need to be developed further to meet the needs of multiple future learning scenarios, such as improving methods for breeding and genetic engineering. In addition, other diverse platforms of food production may offer unrealized potential, such as underutilized terrestrial and aquatic species as alternative sources of nutrition and biomass production. We demonstrate that although several methods or traits could facilitate a more efficient crop production system in some of the scenarios, others may offer great potential in all four of the future learning scenarios. Altogether, this indicates that depending on which future we are heading toward, distinct plant research fields should be given priority if we are to meet our food, feed and non‐food biomass production needs in the coming decades.

This study aims to evaluate the abdominal aortic atherosclerotic plaque index (API)’s predictive role in patients with pre-operatively or post-operatively developed chronic kidney disease (CKD) treated with robot-assisted partial nephrectomy (RAPN) for renal cell carcinoma (RCC). One hundred and eighty-three patients (134 with no pre- and post-operative CKD (no CKD) and 49 with persistent or post-operative CKD development (post-op CKD)) who underwent RAPN between January 2019 and January 2022 were deemed eligible for the analysis. The API was calculated using dedicated software by assessing the ratio between the CT scan atherosclerotic plaque volume and the abdominal aortic volume. The ROC regression model demonstrated the influence of API on CKD development, with an increasing effect according to its value (coefficient 0.13; 95% CI 0.04–0.23; p = 0.006). The Model 1 multivariable analysis of the predictors of post-op CKD found that the following are independently associated with post-op CKD: Charlson Comorbidity Index (OR 1.31; p = 0.01), last follow-up (FU) Δ%eGFR (OR 0.95; p < 0.01), and API ≥ 10 (OR 25.4; p = 0.01). Model 2 showed API ≥ 10 as the only factor associated with CKD development (OR 25.2; p = 0.04). The median follow-up was 22 months. Our results demonstrate API to be a strong predictor of post-operative CKD, allowing the surgeon to tailor the best treatment for each patient, especially in those who might be at higher risk of CKD.

Abstract Background Precision genome mutagenesis using CRISPR/Cas has become the standard method to generate mutant plant lines. Several improvements have been made to increase mutagenesis efficiency, either through vector optimisation or the application of heat stress. Results Here, we present a simplified heat stress assay that can be completed in six days using commonly-available laboratory equipment. We show that three heat shocks (3xHS) efficiently increases indel efficiency of LbCas12a and Cas9, irrespective of the target sequence or the promoter used to express the nuclease. The generated indels are primarily somatic, but for three out of five targets we demonstrate that up to 25% more biallelic mutations are transmitted to the progeny when heat is applied compared to non-heat controls. We also applied our heat treatment to lines containing CRISPR base editors and observed a 22-27% increase in the percentage of C-to-T base editing. Furthermore, we test the effect of 3xHS on generating large deletions and a homologous recombination reporter. Interestingly, we observed no positive effect of 3xHS treatment on either approach using our conditions. Conclusions Together, our experiments show that heat treatment is consistently effective at increasing the number of somatic mutations using many CRISPR approaches in plants and in some cases can increase the recovery of mutant progeny.

Abstract Rapid increase of product titers in upstream processes has presented challenges for downstream processing, where purification costs increase linearly with the increase of the product yield. Hence, innovative solutions are becoming increasingly popular. Process Analytical Technology (PAT) tools, such as spectroscopic techniques, are on the rise due to their capacity to provide real‐time, precise analytics. This ensures consistent product quality and increased process understanding, as well as process control. Mid‐infrared spectroscopy (MIR) has emerged as a highly promising technique within recent years, owing to its ability to monitor several critical process parameters at the same time and unchallenging spectral analysis and data interpretation. For in‐line monitoring, Attenuated Total Reflectance—Fourier Transform Infrared Spectroscopy (ATR‐FTIR) is a method of choice, as it enables reliable measurements in a liquid environment, even though water absorption bands are present in the region of interest. Here, we present MIR spectroscopy as a monitoring tool of critical process parameters in ultrafiltration/diafiltration (UFDF). MIR spectrometer was integrated in the UFDF process in an in‐line fashion through a single‐use flow cell containing a single bounce silicon ATR crystal. The results indicate that the one‐point calibration algorithm applied to the MIR spectra, predicts highly accurate protein concentrations, as compared with validated offline analytical methods.

Abstract The world needs more than double its current agricultural productivity by 2050 to produce enough food and feed, as well as to provide feedstock for the bioeconomy. These future increases will not only need to be sustainable but without comprommising the nutritional quality, and ideally also need to decrease greenhouse gas emissions and increase carbon sequestration to help mitigate the consequences of global climate change. These challenges could be tackled by developing and integrating new future‐proof crops into our food system. The H2020 CropBooster‐P project sets out plant‐centered breeding approaches guided by a broad socio‐economic and societal support. First, the potential approaches for breeding crops with sustainably increased yields adapted to the future climate of Europe are identified. These crop‐breeding options are subsequently prioritized and their adoption considered by experts across the agri‐food system and the wider public, taking into account environmental, economic and other technical criteria. In this way, a specific research agenda to future‐proof our crops was developed, supported by an eventual implementation plan.

Abstract The growing world population and global increases in the standard of living both result in an increasing demand for food, feed and other plant‐derived products. In the coming years, plant‐based research will be among the major drivers ensuring food security and the expansion of the bio‐based economy. Crop productivity is determined by several factors, including the available physical and agricultural resources, crop management, and the resource use efficiency, quality and intrinsic yield potential of the chosen crop. This review focuses on intrinsic yield potential, since understanding its determinants and their biological basis will allow to maximize the plant's potential in food and energy production. Yield potential is determined by a variety of complex traits that integrate strictly regulated processes and their underlying gene regulatory networks. Due to this inherent complexity, numerous potential targets have been identified that could be exploited to increase crop yield. These encompass diverse metabolic and physical processes at the cellular, organ and canopy level. We present an overview of some of the distinct biological processes considered to be crucial for yield determination that could further be exploited to improve future crop productivity.