Exploring the effects of ageing on instrumental and sensory characteristics of meat from Lidia breed females: A comparative study of two commercial types.

The aim of this study was to assess the influence of ageing on instrumental and sensory qualities in Longissimus thoracis et lumborum (LTL) from heifers (n = 200) and cows (n = 100) of Lidia breed. The animals were slaughtered as heifers (24-48 months) or cull cows (> 48 months). For instrumental analysis, pars Thoracis aged at 7, 14 and 28 days was used; for sensory analysis, pars Lumborum aged at 14 and 28 days was evaluated. Heifers showed redder and yellower meat (P < 0.05) and cows showed slightly higher Water Holding Capacity (WHC): Thawing Loss (TL) = P < 0.05; Drip Loss (DL) = P < 0.01; Pressure Loss (PL) = P < 0.01; Cooking Loss (CL) = P < 0.05. Ageing generated changes in meat colour, with increases in lightness (L*, linear pattern, P < 0.001) and oscillations in a* and b* (quadratic patterns; P < 0.05 and P < 0.001, respectively). Ageing affected TL (increasing, P < 0.001) and PL (decreasing, P < 0.05), and generated a significant improvement in Warner Bratzler Shear Force (WBSF) values (P < 0.001). Commercial type revealed changes in consumer panel ratings for flavour (P < 0.05), juiciness (P < 0.01), tenderness (P < 0.001) and overall acceptability (P < 0.001), with better results in these parameters for cull cows. In contrast to the usual, ageing did not affect the sensory traits. There was no significant interaction between commercial type and ageing time, except for beef flavour, which worsened with ageing (P < 0.05).

The DNA Damage Repair Function of Fission Yeast CK1 Involves Targeting Arp8, a Subunit of the INO80 Chromatin Remodeling Complex.

The CK1 family are conserved serine/threonine kinases with numerous substrates and cellular functions. The fission yeast CK1 orthologues Hhp1 and Hhp2 were first characterized as regulators of DNA repair, but the mechanism(s) by which CK1 activity promotes DNA repair had not been investigated. Here, we found that deleting Hhp1 and Hhp2 or inhibiting CK1 catalytic activities in yeast or in human cells increased double-strand breaks (DSBs). The primary pathways to repair DSBs, homologous recombination and nonhomologous end joining, were both less efficient in cells lacking Hhp1 and Hhp2 activity. To understand how Hhp1 and Hhp2 promote DNA damage repair, we identified new substrates of these enzymes using quantitative phosphoproteomics. We confirmed that Arp8, a component of the INO80 chromatin remodeling complex, is a bona fide substrate of Hhp1 and Hhp2 important for DNA repair. Our data suggest that Hhp1 and Hhp2 facilitate DNA repair by phosphorylating multiple substrates, including Arp8.

Risk of metachronous neoplasia in early-onset colorectal cancer: meta-analysis.

BACKGROUND: Metachronous colorectal cancer refers to patients developing a second colorectal neoplasia diagnosed at least 6 months after the initial cancer diagnosis, excluding recurrence. The aim of this systematic review is to assess the incidence of metachronous colorectal cancer in early-onset colorectal cancer (defined as age at diagnosis of less than 50 years) and to identify risk factors. METHODS: This is a systematic review and meta-analysis performed following the PRISMA statement and registered on PROSPERO. The literature search was conducted in PubMed and Embase. Only studies involving patients with early-onset colorectal cancer (less than 50 years old) providing data on metachronous colorectal cancer were included in the analysis. The primary endpoint was the risk of metachronous colorectal cancer in patients with early-onset colorectal cancer. Secondary endpoints were association with Lynch syndrome, family history and microsatellite instability. RESULTS: Sixteen studies met the inclusion criteria. The incidence of metachronous colorectal cancer was 2.6% (95% c.i. 2.287-3.007). The risk of developing metachronous colorectal cancer in early-onset colorectal cancer versus non-early-onset colorectal cancer patients demonstrated an OR of 0.93 (95% c.i. 0.760-1.141). The incidence of metachronous colorectal cancer in patients with Lynch syndrome was 18.43% (95% c.i. 15.396-21.780), and in patients with family history 10.52% (95% c.i. 5.555-17.659). The proportion of metachronous colorectal cancer tumours in the microsatellite instability population was 19.7% (95% c.i. 13.583-27.2422). CONCLUSION: The risk of metachronous colorectal cancer in patients with early-onset colorectal cancer is comparable to those with advanced age, but it is higher in patients with Lynch syndrome, family history and microsatellite instability. This meta-analysis demonstrates the need to personalize the management of patients with early-onset colorectal cancer according to their risk factors.

Advancing early onset colorectal cancer research: research advocacy, health disparities, and scientific imperatives.

Early onset colorectal cancer (EOCRC) emerged as the fourth foremost contributor to cancer-related mortality among both genders in the late 1990s. Presently, EOCRC (<50) ranks as the leading cause of cancer mortality in men and the second leading cause in women within the United States. Similar trends are now also evident globally, particularly in developed countries. Furthermore, there is strong evidence confirming that health disparities persist in the diagnosis and treatment of EOCRC, with signs indicating that these gaps may worsen in specific cases. These alarming trends highlight the critical need for research to inform evidence-based interventions to reduce the burden of EOCRC globally. Fight Colorectal Cancer (Fight CRC) is the leading patient advocacy group in the United States providing information on colon and rectal cancer research, prevention, treatment, and policy. It is the opinion of Fight CRC that an international, coordinated effort with the medical, research, scientific, advocacy, industry and funding community is needed to advance impactful research. Fight CRC, in partnership with José Perea, MD, PhD, of the Institute of Biomedical Research of Salamanca (IBSAL) in Spain, and partners, are working together to address this global phenomenon and are presenting a multi-faceted research approach to move the field forward.

Addressing the Rising Trend in Early-Age-Onset Cancers in Canada.

A multi-disciplinary symposium on early-age onset cancer (EAOC) was held in October 2023 to explore challenges experienced by this rapidly growing population. A major outcome of the symposium was recognition of the remarkable similarities of EAOC patients' journeys across cancer sites. Prevention and early detection of cancer are hindered by a lack of awareness among patients and family doctors that cancer can and does occur in younger persons. Distinct characteristics of the disease-such as a later stage at diagnosis and more aggressive tumor biology-require more potent treatments, which result in profound physical and psychosocial consequences that are unique to this age group. EAOC patient empowerment emerged as another key theme of the symposium. The development of a greater number of specialized clinics was called for, and patient support groups were recognized for the vital role they play in empowering patients and their families. Leading-edge medical advancements hold tremendous hope across the spectrum of EAOC care. New technologies based on genomic profiling, immunotherapy and microbiome alteration contribute to the development of highly effective, personalized approaches to treatment. All symposium participants expressed their commitment to speak with one resounding voice to advocate for equitable access to leading care practices for EAOC patients; thus, a fourth symposium is planned for November 2024.

Red Flag Signs and Symptoms for Patients With Early-Onset Colorectal Cancer: A Systematic Review and Meta-Analysis.

Importance: Early-onset colorectal cancer (EOCRC), defined as a diagnosis at younger than age 50 years, is increasing, and so-called red flag signs and symptoms among these individuals are often missed, leading to diagnostic delays. Improved recognition of presenting signs and symptoms associated with EOCRC could facilitate more timely diagnosis and impact clinical outcomes. Objective: To report the frequency of presenting red flag signs and symptoms among individuals with EOCRC, to examine their association with EOCRC risk, and to measure variation in time to diagnosis from sign or symptom presentation. Data Sources: PubMed/MEDLINE, Embase, CINAHL, and Web of Science were searched from database inception through May 2023. Study Selection: Studies that reported on sign and symptom presentation or time from sign and symptom presentation to diagnosis for patients younger than age 50 years diagnosed with nonhereditary CRC were included. Data Extraction and Synthesis: Data extraction and quality assessment were performed independently in duplicate for all included studies using Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guidelines. Joanna Briggs Institute Critical Appraisal tools were used to measure risk of bias. Data on frequency of signs and symptoms were pooled using a random-effects model. Main Outcomes and Measures: Outcomes of interest were pooled proportions of signs and symptoms in patients with EOCRC, estimates for association of signs and symptoms with EOCRC risk, and time from sign or symptom presentation to EOCRC diagnosis. Results: Of the 12 859 unique articles initially retrieved, 81 studies with 24 908 126 patients younger than 50 years were included. The most common presenting signs and symptoms, reported by 78 included studies, were hematochezia (pooled prevalence, 45% [95% CI, 40%-50%]), abdominal pain (pooled prevalence, 40% [95% CI, 35%-45%]), and altered bowel habits (pooled prevalence, 27% [95% CI, 22%-33%]). Hematochezia (estimate range, 5.2-54.0), abdominal pain (estimate range, 1.3-6.0), and anemia (estimate range, 2.1-10.8) were associated with higher EOCRC likelihood. Time from signs and symptoms presentation to EOCRC diagnosis was a mean (range) of 6.4 (1.8-13.7) months (23 studies) and a median (range) of 4 (2.0-8.7) months (16 studies). Conclusions and Relevance: In this systematic review and meta-analysis of patients with EOCRC, nearly half of individuals presented with hematochezia and abdominal pain and one-quarter with altered bowel habits. Hematochezia was associated with at least 5-fold increased EOCRC risk. Delays in diagnosis of 4 to 6 months were common. These findings highlight the need to identify concerning EOCRC signs and symptoms and complete timely diagnostic workup, particularly for individuals without an alternative diagnosis or sign or symptom resolution.

Synthetic Knockout Protein Standard for Evaluating Interference in Tandem Mass Tag-Based Proteomics.

Isobaric labeling is widely used for unbiased, proteome-wide studies, and it provides several advantages, such as fewer missing values among samples and higher quantitative precision. However, ion interference may lead to compressed or distorted observed ratios due to the coelution and coanalysis of peptides. Here, we introduced a synthetic KnockOut standard (sKO) for evaluating interference in tandem mass tags-based proteomics. sKO is made by mixing TMTpro-labeled tryptic peptides derived from four nonhuman proteins and a whole human proteome as background at different proportions. We showcased the utility of the sKO standard by exploring ion interference at different peptide concentrations (up to a 30-fold change in abundance) and using a variety of mass spectrometer data acquisition strategies. We also demonstrated that the sKO standard could provide valuable information for the rational design of acquisition strategies to achieve optimal data quality and discussed its potential applications for high-throughput proteomics workflows development.

Carcass and Meat Quality Traits in Female Lidia Cattle Slaughtered at Different Ages.

The aim of this study was to assess the carcass and meat quality of female Lidia cattle slaughtered at different ages, in order to deepen our understanding of the breed's unique characteristics. The effect of slaughter age on carcass traits and meat quality attributes of m. Longissimus was investigated in Lidia heifers (n = 200) and cows (n = 100) reared and finished in an extensive system. The animals were slaughtered at 24-36 months (Heifer I), 36-48 months (Heifer II) or >48 months (Cull cow). The carcasses (~120 kg) presented poor conformation (O, O+) and medium fatness (2, 2+). The dissection of the 6th rib yielded mean values of 58.6%, 14.3% and 24.8% for lean, fat and bone, respectively. The cows had a higher proportion of dissectible fat (p < 0.05). Subcutaneous fat was classified as dark and yellowish, and meat (aged for 21 days) as dark (L* = 25.5), reddish (a* = 14.4) and moderately yellowish (b* = 12.9), with acceptable water-holding capacity (TL = 5.34%; DL = 0.97%; PL = 8.9%; CL = 22.1%) and intermediate tenderness (WBSF = 4.6 kg/cm2). The b* value of meat was higher (p < 0.05) in cull cows. The meat of cull cows was more yellowish (p < 0.05) and obtained higher scores for flavor (p < 0.05), juiciness p < 0.01), overall tenderness (p < 0.001) and overall acceptance (p < 0.001).

Exploring Breed-Specific Milk Coagulation in Spanish Dairy Sheep: A Canonical Correlation Approach.

The transformation of milk into cheese largely depends on the technological properties of the raw material, with breed being a crucial factor that influences both the composition and coagulation properties of the milk used for cheesemaking. This study uses canonical correlation analysis to explore the relationships between physicochemical traits and coagulation properties in milk from various Spanish breeds, aiming to identify both common and breed-specific patterns that impact milk technological aptitude. A total of 832 milk samples from Manchega, Assaf, Merino de Grazalema, and Merino de Los Pedroches breeds were analyzed. The milk characteristics investigated included pH, composition (fat, protein, lactose, total solids), and coagulation properties (curd firmness-A60, rennet clotting time-RCT, curd firming time-k20, and individual laboratory curd yield-ILCY). The results reveal a shared correlation structure across breeds and unique covariation patterns in some breeds that deviate from the general trend. While Assaf and Merino de Los Pedroches follow the common correlation pattern, Manchega and Merino de Grazalema exhibit distinct patterns. This research underscores the need for in-depth study and suggests that the dairy industry could benefit from shifting from the traditional focus on maximizing fat and protein for higher curd yields to considering technological traits for selective breeding.

A Stochastic Frontier Approach to Study the Relationship between the Hygienic Quality of Bulk Tank Sheep Milk and Technical Efficiency of the Coagulation Process.

Sheep milk from local breeds is important for the production of high-quality cheeses throughout the Mediterranean region, such as Manchego cheese in Spain. To maintain sustainable and efficient production, it is necessary to reach a better understanding of how the composition and hygiene of the milk affect the coagulation process, with the aim of optimizing production yield. This study implemented a stochastic production frontier function to estimate the potential production of curd and efficiency using data from the four seasons of a study of 77 Manchega sheep farms. The Cobb-Douglas production frontier model was estimated using the maximum likelihood estimation method. The results showed that the content of protein, lactose, and fat exhibited increasing returns to scale, with protein content being the most significant factor for curd production. Approximately half of the inefficiency was due to factors related to the technological properties and the hygiene of the milk. The pH, curd firmness, and concentration of lactic acid bacteria improved the efficiency of coagulation, while the concentration of spores of lactate-fermenting Clostridium spp., Pseudomonas spp., staphylococci, and catalase-negative gram-positive cocci favored the inefficiency of the coagulation process. To date, this is the first study to evaluate the effect of different factors, such as microbial groups, milk composition, and technological properties, on the efficiency of the coagulation process in dairy sheep.

Associations between Milk Coagulation Properties and Microbiological Quality in Sheep Bulk Tank Milk.

This study conducted a seasonal analysis of bulk tank milk from 77 sheep farms to establish relationships between the concentration of major microbial groups and milk coagulation properties. The investigated milk traits included composition (pH, fat, casein, lactose), coagulation properties (curd firmness: A60-, rennet clotting time: RCT-, curd firming time: k20-, curd yield: CY-), and somatic cell score (SCS). The main microbial groups analyzed were total mesophilic bacteria (SPC), thermodurics (THERMO), psychrotrophs (PSYCHRO), Pseudomonas spp. (PSEUDO), lactic acid bacteria (LAB), catalase-negative gram-positive cocci (GPCNC), Escherichia coli (ECOLI), coliforms other than Escherichia coli (COLI), coagulase-positive staphylococci (CPS), coagulase-negative staphylococci (CNS), and spores of lactate-fermenting Clostridium (BAB). Mixed linear models were used to explore associations between coagulation properties and the aforementioned variables. Results demonstrated that incorporating microbial loads into the models improves their fit and the relative quality of the outcomes. An important seasonality is demonstrated by an increase in CY and A60, along with a decrease in RCT and k20 during autumn and winter, contrasting with spring and summer. BAB concentration resulted in a reduction of A60 and an increase in RCT, whereas SPC concentration led to an enhancement of A60 and a reduction in RCT. An increase in GPCNC concentration was associated with an increase in k20 and a decrease in CY.

Exploring Interrelationships between Colour, Composition, and Coagulation Traits of Milk from Cows, Goats, and Sheep.

This study explores the interrelationships between the composition, coagulation, and colour of sheep, goat, and cow milk to identify their similarities and differences and to assess whether the relationships between the variables are common to all species or whether they emerge from species-specific relationships. For this purpose, 2400 individual milk samples were analysed. The differences and similarities between the species were determined using discriminant analysis and cluster analysis. The results show a clear differentiation between species. Sheep milk stands out for its cheesemaking capacity and shows similarities with goat milk in composition and coagulation. Nonetheless, colorimetry highlights a greater similarity between sheep and cow milk. Composition and colorimetry were more discriminating than coagulation, and the variables that differed the most were fat, protein, curd yield, lightness, and red-green balance. Using canonical correlation, the interrelationships between the different sets of variables were explored, revealing patterns of common variation and species-specific relationships. Colorimetric variables were closely related to milk solids in all species, while in sheep milk, an inverse relationship with lactose was also identified. Furthermore, a strong relationship was revealed for all species between colour and curd yield. This could be modelled and applied to estimate the technological value of milk, proving colorimetry as a useful tool for the dairy industry.

Ultrafast bisulfite sequencing detection of 5-methylcytosine in DNA and RNA.

Bisulfite sequencing (BS-seq) to detect 5-methylcytosine (5mC) is limited by lengthy reaction times, severe DNA damage, overestimation of 5mC level and incomplete C-to-U conversion of certain DNA sequences. We present ultrafast BS-seq (UBS-seq), which uses highly concentrated bisulfite reagents and high reaction temperatures to accelerate the bisulfite reaction by ~13-fold, resulting in reduced DNA damage and lower background noise. UBS-seq allows library construction from small amounts of purified genomic DNA, such as from cell-free DNA or directly from 1 to 100 mouse embryonic stem cells, with less overestimation of 5mC level and higher genome coverage than conventional BS-seq. Additionally, UBS-seq quantitatively maps RNA 5-methylcytosine (m5C) from low inputs of mRNA and allows the detection of m5C stoichiometry in highly structured RNA sequences. Our UBS-seq results identify NSUN2 as the major 'writer' protein responsible for the deposition of ~90% of m5C sites in HeLa mRNA and reveal enriched m5C sites in 5'-regions of mammalian mRNA, which may have functional roles in mRNA translation regulation.

Topological Data Analysis of Electroencephalogram Signals for Pediatric Obstructive Sleep Apnea.

Topological data analysis (TDA) is an emerging technique for biological signal processing. TDA leverages the invariant topological features of signals in a metric space for robust analysis of signals even in the presence of noise. In this paper, we leverage TDA on brain connectivity networks derived from electroencephalogram (EEG) signals to identify statistical differences between pediatric patients with obstructive sleep apnea (OSA) and pediatric patients without OSA. We leverage a large corpus of data, and show that TDA enables us to see a statistical difference between the brain dynamics of the two groups.Clinical relevance- This establishes the potential of topological data analysis as a tool to identify obstructive sleep apnea without requiring a full polysomnogram study, and provides an initial investigation towards easier and more scalable obstructive sleep apnea diagnosis.

Lights and shadows in the early-onset colorectal cancer management and research: An integrative perspective - Physician scientist with patient advocates.

Early-onset colorectal cancer (age under 50 years) (EOCRC) is an entity of undeniable importance, both because of its growing incidence, and the population it affects. Other current reviews emphasize the essential points regarding the clinical management and knowledge of its molecular bases. However, we intend to go one step further. With the increased significance of patient participation and disease experience in mind, we have integrated the voice of the patient to show the weaknesses and the needs, and next steps in the advancement of knowledge and management of EOCRC. This integrative review of the different perspectives, clinical, research and the patients themselves, can therefore be defined as an integrative needs assessment. Hence, this may be a first step in working towards an essential homogeneity of definitions and action.

Fission yeast CK1 promotes DNA double-strand break repair through both homologous recombination and non-homologous end joining.

The CK1 family are conserved serine/threonine kinases with numerous substrates and cellular functions. The fission yeast CK1 orthologues Hhp1 and Hhp2 were first characterized as regulators of DNA repair, but the mechanism(s) by which CK1 activity promotes DNA repair had not been investigated. Here, we found that deleting Hhp1 and Hhp2 or inhibiting CK1 catalytic activities in yeast or in human cells activated the DNA damage checkpoint due to persistent double-strand breaks (DSBs). The primary pathways to repair DSBs, homologous recombination and non-homologous end joining, were both less efficient in cells lacking Hhp1 and Hhp2 activity. In order to understand how Hhp1 and Hhp2 promote DSB repair, we identified new substrates using quantitative phosphoproteomics. We confirmed that Arp8, a component of the INO80 chromatin remodeling complex, is a bona fide substrate of Hhp1 and Hhp2 that is important for DSB repair. Our data suggest that Hhp1 and Hhp2 facilitate DSB repair by phosphorylating multiple substrates, including Arp8.

Sample multiplexing-based targeted pathway proteomics with real-time analytics reveals the impact of genetic variation on protein expression.

Targeted proteomics enables hypothesis-driven research by measuring the cellular expression of protein cohorts related by function, disease, or class after perturbation. Here, we present a pathway-centric approach and an assay builder resource for targeting entire pathways of up to 200 proteins selected from >10,000 expressed proteins to directly measure their abundances, exploiting sample multiplexing to increase throughput by 16-fold. The strategy, termed GoDig, requires only a single-shot LC-MS analysis, ~1 µg combined peptide material, a list of up to 200 proteins, and real-time analytics to trigger simultaneous quantification of up to 16 samples for hundreds of analytes. We apply GoDig to quantify the impact of genetic variation on protein expression in mice fed a high-fat diet. We create several GoDig assays to quantify the expression of multiple protein families (kinases, lipid metabolism- and lipid droplet-associated proteins) across 480 fully-genotyped Diversity Outbred mice, revealing protein quantitative trait loci and establishing potential linkages between specific proteins and lipid homeostasis.