Electron Transfer Function versus Oxygen Delivery: A Comparative Study for Several Hexacoordinated Globins Across the Animal Kingdom

Caenorhabditis elegans globin GLB-26 (expressed from gene T22C1.2) has been studied in comparison with human neuroglobin (Ngb) and cytoglobin (Cygb) for its electron transfer properties. GLB-26 exhibits no reversible binding for O2 and a relatively low CO affinity compared to myoglobin-like globins. These differences arise from its mechanism of gaseous ligand binding since the heme iron of GLB-26 is strongly hexacoordinated in the absence of external ligands; the replacement of this internal ligand, probably the E7 distal histidine, is required before binding of CO or O2 as for Ngb and Cygb. Interestingly the ferrous bis-histidyl GLB-26 and Ngb, another strongly hexacoordinated globin, can transfer an electron to cytochrome c (Cyt-c) at a high bimolecular rate, comparable to those of inter-protein electron transfer in mitochondria. In addition, GLB-26 displays an unexpectedly rapid oxidation of the ferrous His-Fe-His complex without O2 actually binding to the iron atom, since the heme is oxidized by O2 faster than the time for distal histidine dissociation. These efficient mechanisms for electron transfer could indicate a family of hexacoordinated globin which are functionally different from that of pentacoordinated globins

Astrocytes: biology and pathology

Astrocytes are specialized glial cells that outnumber neurons by over fivefold. They contiguously tile the entire central nervous system (CNS) and exert many essential complex functions in the healthy CNS. Astrocytes respond to all forms of CNS insults through a process referred to as reactive astrogliosis, which has become a pathological hallmark of CNS structural lesions. Substantial progress has been made recently in determining functions and mechanisms of reactive astrogliosis and in identifying roles of astrocytes in CNS disorders and pathologies. A vast molecular arsenal at the disposal of reactive astrocytes is being defined. Transgenic mouse models are dissecting specific aspects of reactive astrocytosis and glial scar formation in vivo. Astrocyte involvement in specific clinicopathological entities is being defined. It is now clear that reactive astrogliosis is not a simple all-or-none phenomenon but is a finely gradated continuum of changes that occur in context-dependent manners regulated by specific signaling events. These changes range from reversible alterations in gene expression and cell hypertrophy with preservation of cellular domains and tissue structure, to long-lasting scar formation with rearrangement of tissue structure. Increasing evidence points towards the potential of reactive astrogliosis to play either primary or contributing roles in CNS disorders via loss of normal astrocyte functions or gain of abnormal effects. This article reviews (1) astrocyte functions in healthy CNS, (2) mechanisms and functions of reactive astrogliosis and glial scar formation, and (3) ways in which reactive astrocytes may cause or contribute to specific CNS disorders and lesions

Potential for large-scale CO2 removal via enhanced rock weathering with croplands

Enhanced silicate rock weathering (ERW), deployable with croplands, has potential use for atmospheric carbon dioxide (CO2) removal (CDR), which is now necessary to mitigate anthropogenic climate change1. ERW also has possible co-benefits for improved food and soil security, and reduced ocean acidification2,3,4. Here we use an integrated performance modelling approach to make an initial techno-economic assessment for 2050, quantifying how CDR potential and costs vary among nations in relation to business-as-usual energy policies and policies consistent with limiting future warming to 2 degrees Celsius5. China, India, the USA and Brazil have great potential to help achieve average global CDR goals of 0.5 to 2 gigatonnes of carbon dioxide (CO2) per year with extraction costs of approximately US$80–180 per tonne of CO2. These goals and costs are robust, regardless of future energy policies. Deployment within existing croplands offers opportunities to align agriculture and climate policy. However, success will depend upon overcoming political and social inertia to develop regulatory and incentive frameworks. We discuss the challenges and opportunities of ERW deployment, including the potential for excess industrial silicate materials (basalt mine overburden, concrete, and iron and steel slag) to obviate the need for new mining, as well as uncertainties in soil weathering rates and land–ocean transfer of weathered products

EFFECTS OF LOW INTENSITY TREADMILL EXERCISE ON MUSCLE WASTING IN THE MALE TUMOR BEARING MOUSE

Louisa Tichy, Jason T. Brantley, Traci L. Parry. University of North Carolina at Greensboro, Greensboro, NC. Background: Cancer cachexia is a multifactorial, metabolic wasting syndrome that is responsible for up to one-third of deaths in cancer patients. While research is growing, there are no clear diagnostic criteria and cancer cachexia remains an untreated condition. Current research shows that exercise interventions could have a positive impact on cancer cachexia by slowing its development. Questions remain regarding the most effective time, duration, and intensity of exercise as a preventative intervention against cancer cachexia. Purpose: The purpose of this study was to determine if low intensity treadmill exercise can act as a protective measure and treatment intervention against cancer-mediated muscle wasting in male mice. Methods: Male LC3 Tg+ mice and WT mice were randomly separated into four groups, sedentary non-tumor bearing (SED+NT), sedentary tumor bearing (SED+T), treadmill exercise non-tumor bearing (Low+NT), and treadmill exercise tumor bearing (Low+T). Mice were injected with tumor cells (T group; 5x105 LLC cells in flank) or remained non-tumor (NT) for 4 weeks. During the 4 weeks, mice underwent a low-intensity treadmill exercise training protocol (Low) or remained sedentary (SED). To examine the protective effects of exercise, grip strength, echocardiography and tumor growth evaluations were taken at baseline and the 4-week time points. Results: Sedentary tumor bearing mice (SED+T) exhibited the worst skeletal muscle function (grip strength) and cardiac function (fractional shortening) compared to all other groups. Low intensity treadmill appeared to protect the musculature since exercised tumor bearing mice (Low+T) showed a preservation of both grip strength and fractional shortening compared to their sedentary counterparts (SED+T). Additionally, treadmill exercise (Low+T) resulted in smaller tumor mass and volume (p=0.066) compared to the SED+T group. Conclusion: Low-intensity treadmill exercise shows potential to preserve skeletal and cardiac muscle function, as well as stunt tumor growth. Therefore, low-intensity treadmill exercise may be an effective, affordable, and accessible treatment intervention for cancer patients. This information is crucial in understanding the significance of exercise in cancer patients and elucidating the importance of timing and intensity of exercise as a protective measure against the detrimental effects of cancer cachexia

Case selection and outcome of radical perineal prostatectomy in localized prostate cancer

Radical prostatectomy continues to play a central role in the management of localized prostate cancer. The majority of patients diagnosed with prostate cancer will undergo radical prostatectomy. A decrease in the morbidity of this surgical procedure has been accomplished through an improved understanding of pelvic anatomy and a greater understanding of the natural history of prostate cancer. Recently, minimally invasive techniques have been applied to radical prostatectomy (laparoscopic prostatectomy) in order to further decrease the morbidity of this operation. What remains to be determined is whether this approach confers the same long term surgical outcomes as the open approach. One method which offers known long term outcomes coupled with decreased morbidity is the radical perineal prostatectomy. The purpose of this paper is to review the criteria for patient selection as well as outcomes of the radical perineal prostatectomy