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Understanding stress tolerance mechanisms opens new opportunities for agricultural applications.

Extremely low birth weight (ELBW) infants are at risk for end-organ hypoxia and ischemia. Dactolisib ic50 Regional tissue oxygenation of the brain and gut as monitored with near-infrared spectroscopy (NIRS) may change with postnatal age, but normal ranges are not well defined.

A prospective study of ELBW preterm infants utilized NIRS monitoring to assess changes in cerebral and mesenteric saturation (Csat and Msat) over the first week after birth. This secondary study of a multicenter trial comparing hemoglobin transfusion thresholds assessed cerebral and mesenteric fractional tissue oxygen extraction (cFTOE and mFTOE) and relationships with perinatal variables.

In 124 infants, both Csat and Msat declined over the first week, with a corresponding increase in oxygen extraction. With lower gestational age, lower birth weight, and 5-min Apgar score ≤5, there was a greater increase in oxygen extraction in the brain compared to the gut. Infants managed with a lower hemoglobin transfusion threshold receiving ≥2 transfusions ≤5.

Simultaneous monitoring of cerebral and mesenteric tissue saturation demonstrates the balance of oxygenation between preterm brain and gut and may inform protective strategies. Over the first week, oxygen saturation of the brain and gut declines as oxygen extraction increases. A low hemoglobin transfusion threshold is associated with lower cerebral saturation and higher cerebral oxygen extraction compared to a high hemoglobin transfusion threshold, although this did not translate into clinically relevant differences in the TOP trial primary outcome. Greater oxygen extraction by the brain compared to the gut occurs with lower gestational age, lower birth weight, and 5-min Apgar score ≤5.

Preterm infants are at enhanced risk of brain injury due to altered cerebral haemodynamics during postnatal transition. This observational study aimed to assess the clinical determinants of transitional cerebrovascular reactivity and its association with intraventricular haemorrhage (IVH).

Preterm infants <32 weeks underwent continuous monitoring of cerebral oxygenation and heart rate over the first 72 h after birth. Serial cranial and cardiac ultrasound assessments were performed to evaluate the ductal status and to diagnose IVH onset. The moving correlation coefficient between cerebral oxygenation and heart rate (TOHRx) was calculated. Linear mixed-effect models were used to analyse the impact of relevant clinical variables on TOHRx. The association between TOHRx and IVH development was also assessed.

Seventy-seven infants were included. A haemodynamically significant patent ductus arteriosus (hsPDA) (β = 0.044, 95% CI 0.007-0.081) and ongoing dopamine treatment (β = 0.096, 95% CI 0.032-0.159) wereoprotective strategies in at-risk preterm infants. The evidence of increased TOHRx in infants developing high-grade compared to low-grade or no IVH during the transitional period further supports the role of impaired cerebrovascular reactivity in IVH pathophysiology.

The correlation coefficient between cerebral oxygenation and heart rate (TOHRx) provides a non-invasive estimation of cerebrovascular reactivity, whose failure has a potential pathogenic role in the development of IVH in preterm infants. This study shows that cerebrovascular reactivity during the transitional period improves over time and is affected by specific clinical and therapeutic factors, whose knowledge could support the development of individualized neuroprotective strategies in at-risk preterm infants. The evidence of increased TOHRx in infants developing high-grade compared to low-grade or no IVH during the transitional period further supports the role of impaired cerebrovascular reactivity in IVH pathophysiology.

The antiviral role of glycosaminoglycans in human milk (HM-GAGs) has been poorly investigated. They are highly sulfated polysaccharides, which were proposed to act as decoy receptors according to their structure. The aim of this study is to evaluate the antiviral potential and the mechanism of action of total and individual HM-GAGs against three pediatric clinically relevant viruses respiratory syncytial virus (RSV), cytomegalovirus (HCMV), and rotavirus.

HM-GAGs were isolated from HM and a library of individual GAGs, structurally related to HM-GAGs, was prepared. The antiviral activity of HM-GAGs and the impact of thermal treatment were investigated in vitro by specific antiviral assays.

We demonstrated that HM-GAGs are endowed with anti-HCMV and anti-RSV activity and that they act by altering virus attachment to cell. We clarified the contribution of individual HM-GAGs, showing a specific structure-related activity. We did not observe any alteration of HM-GAG antiviral activity after thermal treatmentd that HM-GAGs are endowed with significant anti-HCMV and anti-RSV activity and that they are able to alter virus binding to the cell. The contribution of individual HM-GAGs is mainly exerted by the FMHep and is not based on a simple charge interaction between the virus and sulfate groups but involves a specific GAG structural configuration. Our results contribute to identifying the multiple factors synergically acting in mediating HM antiviral properties and to clarifying their specific mechanism of action.There is an ongoing societal debate about plant breeding systems and their impact on stakeholders in food systems. Hybrid breeding and hybrid seed have become controversial topics as they are believed to mostly serve high-tech agricultural systems. This article focuses on the perspective of commercial plant breeders when developing new cultivars of food crops. Arguably, hybrid breeding is the most effective breeding system for genetic improvement of crops, enhancing yields, improving product quality and increasing resistance against (a)biotic stresses. Nonetheless, hybrid breeding is not commercially applied in all crops. We analyse how biological and economic factors determine whether a commercial plant breeder opts for the hybrid system or not. We show that the commercial feasibility of hybrid breeding depends on the crop and business case. In conclusion, the commercial application of hybrid breeding in crops seems to be hampered mostly by high costs of seed production. Case studies regarding the hybrid transitions in maize, wheat and potato are included to illustrate these findings.A limited number of studies have described patients on finasteride showing findings which were consistent with Peyronie's disease (PD). We aimed to detect a pharmacovigilance signal of possible association between finasteride and PD-related clinical features. The Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database was queried to identify the ten drugs which were associated the most with the adverse drug reactions (ADRs) recorded as "penile curvature" and/or "Peyronie's disease". A similar analysis, including the same drugs, was carried out for the EMA (European Medicines Agency) EudraVigilance (EV) database. Descriptive data have been analyzed, and Proportional Reporting Ratios (PRRs) have been computed against the other nine drugs of the database. Overall, 860 reports of "penile curvature" and/or "Peyronie's disease", were identified in the FAERS database, 214 of which (24.9%) were associated with finasteride. Most reports (56.9%) were submitted by healthcare professionals. Where a treatment-indication was stated, the vast majority of reports (176/210; 83.8%) were associated with androgenetic alopecia. The outcome of most ADRs was "serious" (82.2%), with 96 ADRs resulting in levels of permanent disability. For 97/214 individual cases, penile curvature/PD reports were not part of a syndromic cluster suggestive of post-finasteride syndrome (PFS). The PRR resulted 6.6 (95% CI 5.6-7.8) and 11.8 (95% CI 9.08-15.33), respectively, in the FAERS and in the EV databases. Notwithstanding the related limitations and biasing factors of pharmacovigilance studies based on spontaneous reporting, the PRR values here identified should be interpreted as strong signals of disproportionality. These findings, per se, are however not useful to confirm any causal association. Clinical studies are needed to investigate on the possible role for finasteride in causing PD-related clinical features, an hypothesis which remains highly speculative due to the very questionable quality of present data.How are haematopoietic stem cells (HSCs) protected from inflammation, which increases with age and can deplete HSCs? Adiponectin, an anti-inflammatory factor that is not required for HSC function or haematopoiesis, promotes stem/progenitor cell proliferation after bacterial infection and myeloablation. Adiponectin binds two receptors, AdipoR1 and AdipoR2, which have ceramidase activity that increases upon adiponectin binding. Here we found that adiponectin receptors are non-cell-autonomously required in haematopoietic cells to promote HSC quiescence and self-renewal. Adiponectin receptor signalling suppresses inflammatory cytokine expression by myeloid cells and T cells, including interferon-γ and tumour necrosis factor. Without adiponectin receptors, the levels of these factors increase, chronically activating HSCs, reducing their self-renewal potential and depleting them during ageing. Pathogen infection accelerates this loss of HSC self-renewal potential. Blocking interferon-γ or tumour necrosis factor signalling partially rescues these effects. Adiponectin receptors are thus required in immune cells to sustain HSC quiescence and to prevent premature HSC depletion by reducing inflammation.Acute trauma stimulates local repair mechanisms but can also impact structures distant from the injury, for example through the activity of circulating factors. To study the responses of remote tissues during tissue regeneration, we profiled transcriptomes of zebrafish brains after experimental cardiac damage. We found that the transcription factor gene cebpd was upregulated remotely in brain ependymal cells as well as kidney tubular cells, in addition to its local induction in epicardial cells. cebpd mutations altered both local and distant cardiac injury responses, altering the cycling of epicardial cells as well as exchange between distant fluid compartments. Genome-wide profiling and transgenesis identified a hormone-responsive enhancer near cebpd that exists in a permissive state, enabling rapid gene expression in heart, brain and kidney after cardiac injury. Deletion of this sequence selectively abolished cebpd induction in remote tissues and disrupted fluid regulation after injury, without affecting its local cardiac expression response. Our findings suggest a model to broaden gene function during regeneration in which enhancer regulatory elements define short- and long-range expression responses to injury.Dynamic morphological changes of intracellular organelles are often regulated by protein phosphorylation or dephosphorylation1-6. Phosphorylation modulates stereospecific interactions among structured proteins, but how it controls molecular interactions among unstructured proteins and regulates their macroscopic behaviours remains unknown. Here we determined the cell cycle-specific behaviour of Ki-67, which localizes to the nucleoli during interphase and relocates to the chromosome periphery during mitosis. Mitotic hyperphosphorylation of disordered repeat domains of Ki-67 generates alternating charge blocks in these domains and increases their propensity for liquid-liquid phase separation (LLPS). A phosphomimetic sequence and the sequences with enhanced charge blockiness underwent strong LLPS in vitro and induced chromosome periphery formation in vivo. Conversely, mitotic hyperphosphorylation of NPM1 diminished a charge block and suppressed LLPS, resulting in nucleolar dissolution. Cell cycle-specific phase separation can be modulated via phosphorylation by enhancing or reducing the charge blockiness of disordered regions, rather than by attaching phosphate groups to specific sites.