Moderate traumatic brain injury is linked to acute behaviour deficits and long term mitochondrial alterations

© 2016 John Wiley & Sons Australia, Ltd Traumatic brain injury (TBI) remains one of the leading causes of death and disability worldwide. Mild TBI may lead to neuropsychiatric sequelae, including memory loss and motor impairment. Mitochondrial dysfunction and oxidative stress have a contributory role in several neurological disorders; however, their association with mitophagy in mild TBI is unclear. TBI was induced in female Sprague Dawley (SD) rats using a New York University Impactor (10 g, impactor head 2.5 mm diameter, weight drop 50 mm) and compared to sham surgery controls. The novel object recognition and error ladder tests were performed at 24 hours and for 6 weeks post injury, and the brains were examined histologically to confirm the extent of injury. Mitochondria manganese superoxide dismutase (MnSOD) and the oxidative phosphorylation (OXPHOS) complexes I-V (CI-CV), as well as mitophagy markers, dynamin related protein 1 (DRP-1), LC3A/B and PTEN-induced putative kinase 1 (PINK-1), were measured in the penumbra by western blot. At 24 hours sham rats performed as expected on a novel object recognition test while TBI rats showed cognitive deficits at the early time points. TBI rats also showed more early motor deficits on a horizontal ladder, compared with the sham rats. MnSOD, OXPHOS CI, CIII and CV protein levels were significantly lower in the TBI group at 24 hours. DRP-1, LC3A/B I and II, and PINK-1 were increased at 6 weeks suggesting abnormal mitophagy. Moderate TBI caused immediate cognitive and mild motor functional deficits in the rats that did not persist. Reduced antioxidative capacity and possibly compromised mitochondrial function may affect the long term functional recovery

Microautophagy of the Nucleus Coincides with a Vacuolar Diffusion Barrier at Nuclear–Vacuolar Junctions

Nuclear-vacuolar (NV) junctions are organelle contact sites in yeast. They exclude nuclear pores from the organelle interface. On the vacuolar side, a lipid-dependent process excludes specific membrane proteins, such as V-ATPase, from the contact site. This suggests that NV junctions establish selective diffusion barriers

The Land-Potential Knowledge System (LandPKS): mobile apps and collaboration for optimizing climate change investments

Massive investments in climate change mitigation and adaptation are projected during coming decades. Many of these investments will seek to modify how land is managed. The return on both types of investments can be increased through an understanding of land potential: the potential of the land to support primary production and ecosystem services, and its resilience. A Land-Potential Knowledge System (LandPKS) is being developed and implemented to provide individual users with point-based estimates of land potential based on the integration of simple, geo-tagged user inputs with cloud-based information and knowledge. This system will rely on mobile phones for knowledge and information exchange, and use cloud computing to integrate, interpret, and access relevant knowledge and information, including local knowledge about land with similar potential. The system will initially provide management options based on long-term land potential, which depends on climate, topography, and relatively static soil properties, such as soil texture, depth, and mineralogy. Future modules will provide more specific management information based on the status of relatively dynamic soil properties such as organic matter and nutrient content, and of weather. The paper includes a discussion of how this system can be used to help distinguish between meteorological and edaphic drought

Under positive pressure: how stakeholder pressure affects corporate social responsibility implementation

This study tests a model that links stakeholder pressure to the implementation of corporate social responsibility (CSR) activities and market performance. Stakeholder groups and competitors might exert pressure on companies to implement CSR, which could lead to positive effects on market performance. Using structural equation modeling (SEM), the authors find that stakeholders and competitors exert pressure differently. The effect of CSR implementation on market performance is moderated by market dynamism: It affects market performance more in dynamic environments. The authors discuss implications for both companies and stakeholders

Relationship of an adherence score with blood pressure control status among patients with hypertension and their determinants: Findings from a nationwide blood pressure screening program

This study aimed to examine the relationship of adherence with blood pressure (BP) control and its associated factors in hypertensive patients. This cross‐ sectional nationwide BP screening study was conducted in Malaysia from May to October 2018. Participants with self‐ declared hypertension completed the Hill‐ Bone Compliance to High Blood Pressure Therapy Scale (Hill‐ Bone CHBPTS) which assesses three important domains of patient behavior to hypertension management namely medication taking, appointment keeping and reduced salt intake. Lower scores indicate better compliance while higher scores indicate otherwise. Participant's body mass index and seated BP were measured based on standard measurement protocol. Determinants of adherence to treatment were analyzed using multiple linear regression. Out of 5167 screened subjects, 1705 were known hypertensives. Of these, 927 (54.4%) answered the Hill‐ Bone CHBPTS and were entered into analysis. The mean age was 59.0 ± 13.2 years, 55.6% were female and 42.2% were Malays. The mean Hill‐ Bone CHBPTS score was 20.4 ± 4.4 (range 14‐ 47), and 52.1% had good adherence. The mean systolic BP and diastolic BP were 136.4 ± 17.9 and 80.6 ± 11.6 mmHg, respectively. BP was controlled in 58.3% of those with good adherence compared to 50.2% in those with poor adherence (p = .014). Based on multiple linear regression analysis, female gender (β = −0.72, 95% confidence interval [CI] −1.30, −0.15, p = .014), older age (β = −0.05, 95% CI −0.07, −0.03, p < .001), and individuals with primary or lower educational level (β = −0.91, 95% CI −1.59, −0.23, p = .009) had better adherence to BP management. Interventional programs targeted at the less adherent groups are needed in order to improve their adherence and BP control

PRPF8-mediated dysregulation of hBrr2 helicase disrupts human spliceosome kinetics and 5\ub4-splice-site selection causing tissue-specific defects

\ua9 The Author(s) 2024.The carboxy-terminus of the spliceosomal protein PRPF8, which regulates the RNA helicase Brr2, is a hotspot for mutations causing retinitis pigmentosa-type 13, with unclear role in human splicing and tissue-specificity mechanism. We used patient induced pluripotent stem cells-derived cells, carrying the heterozygous PRPF8 c.6926 A &gt; C (p.H2309P) mutation to demonstrate retinal-specific endophenotypes comprising photoreceptor loss, apical-basal polarity and ciliary defects. Comprehensive molecular, transcriptomic, and proteomic analyses revealed a role of the PRPF8/Brr2 regulation in 5’-splice site (5’SS) selection by spliceosomes, for which disruption impaired alternative splicing and weak/suboptimal 5’SS selection, and enhanced cryptic splicing, predominantly in ciliary and retinal-specific transcripts. Altered splicing efficiency, nuclear speckles organisation, and PRPF8 interaction with U6 snRNA, caused accumulation of active spliceosomes and poly(A)+ mRNAs in unique splicing clusters located at the nuclear periphery of photoreceptors. Collectively these elucidate the role of PRPF8/Brr2 regulatory mechanisms in splicing and the molecular basis of retinal disease, informing therapeutic approaches