Noncovalent Interactions of Hydrated DNA and RNA Mapped by 2D-IR Spectroscopy

Biomolecules couple to their aqueous environment through a variety of noncovalent interactions. Local structures at the surface of DNA and RNA are frequently determined by hydrogen bonds with water molecules, complemented by non-specific electrostatic and many-body interactions. Structural fluctuations of the water shell result in fluctuating Coulomb forces on polar and/or ionic groups of the biomolecular structure and in a breaking and reformation of hydrogen bonds. Two-dimensional infrared (2D-IR) spectroscopy of vibrational modes of DNA and RNA gives insight into local hydration geometries, elementary molecular dynamics, and the mechanisms behind them. In this chapter, recent results from 2D-IR spectroscopy of native and artificial DNA and RNA are presented, together with theoretical calculations of molecular couplings and molecular dynamics simulations. Backbone vibrations of DNA and RNA are established as sensitive noninvasive probes of the complex behavior of hydrated helices. The results reveal the femtosecond fluctuation dynamics of the water shell, the short-range character of Coulomb interactions, and the strength and fluctuation amplitudes of interfacial electric fields.Comment: To appear as Chapter 8 of Springer Series in Optical Sciences: Coherent Multidimensional Spectroscopy -- Editors: Cho, Minhaeng (Ed.), 201

Protein tyrosine phosphatases expression during development of mouse superior colliculus

Protein tyrosine phosphatases (PTPs) are key regulators of different processes during development of the central nervous system. However, expression patterns and potential roles of PTPs in the developing superior colliculus remain poorly investigated. In this study, a degenerate primer-based reverse transcription-polymerase chain reaction (RT-PCR) approach was used to isolate seven different intracellular PTPs and nine different receptor-type PTPs (RPTPs) from embryonic E15 mouse superior colliculus. Subsequently, the expression patterns of 11 PTPs (TC-PTP, PTP1C, PTP1D, PTP-MEG2, PTP-PEST, RPTPJ, RPTPε, RPTPRR, RPTPσ, RPTPκ and RPTPγ) were further analyzed in detail in superior colliculus from embryonic E13 to postnatal P20 stages by quantitative real-time RT-PCR, Western blotting and immunohistochemistry. Each of the 11 PTPs exhibits distinct spatiotemporal regulation of mRNAs and proteins in the developing superior colliculus suggesting their versatile roles in genesis of neuronal and glial cells and retinocollicular topographic mapping. At E13, additional double-immunohistochemical analysis revealed the expression of PTPs in collicular nestin-positive neural progenitor cells and RC-2-immunoreactive radial glia cells, indicating the potential functional importance of PTPs in neurogenesis and gliogenesis

Protein tyrosine phosphatases in glioma biology

Gliomas are a diverse group of brain tumors of glial origin. Most are characterized by diffuse infiltrative growth in the surrounding brain. In combination with their refractive nature to chemotherapy this makes it almost impossible to cure patients using combinations of conventional therapeutic strategies. The drastically increased knowledge about the molecular underpinnings of gliomas during the last decade has elicited high expectations for a more rational and effective therapy for these tumors. Most studies on the molecular pathways involved in glioma biology thus far had a strong focus on growth factor receptor protein tyrosine kinase (PTK) and phosphatidylinositol phosphatase signaling pathways. Except for the tumor suppressor PTEN, much less attention has been paid to the PTK counterparts, the protein tyrosine phosphatase (PTP) superfamily, in gliomas. PTPs are instrumental in the reversible phosphorylation of tyrosine residues and have emerged as important regulators of signaling pathways that are linked to various developmental and disease-related processes. Here, we provide an overview of the current knowledge on PTP involvement in gliomagenesis. So far, the data point to the potential implication of receptor-type (RPTPδ, DEP1, RPTPμ, RPTPζ) and intracellular (PTP1B, TCPTP, SHP2, PTPN13) classical PTPs, dual-specific PTPs (MKP-1, VHP, PRL-3, KAP, PTEN) and the CDC25B and CDC25C PTPs in glioma biology. Like PTKs, these PTPs may represent promising targets for the development of novel diagnostic and therapeutic strategies in the treatment of high-grade gliomas

Neuroprotection by adenosine in the brain: From A1 receptor activation to A2A receptor blockade

Adenosine is a neuromodulator that operates via the most abundant inhibitory adenosine A1 receptors (A1Rs) and the less abundant, but widespread, facilitatory A2ARs. It is commonly assumed that A1Rs play a key role in neuroprotection since they decrease glutamate release and hyperpolarize neurons. In fact, A1R activation at the onset of neuronal injury attenuates brain damage, whereas its blockade exacerbates damage in adult animals. However, there is a down-regulation of central A1Rs in chronic noxious situations. In contrast, A2ARs are up-regulated in noxious brain conditions and their blockade confers robust brain neuroprotection in adult animals. The brain neuroprotective effect of A2AR antagonists is maintained in chronic noxious brain conditions without observable peripheral effects, thus justifying the interest of A2AR antagonists as novel protective agents in neurodegenerative diseases such as Parkinson’s and Alzheimer’s disease, ischemic brain damage and epilepsy. The greater interest of A2AR blockade compared to A1R activation does not mean that A1R activation is irrelevant for a neuroprotective strategy. In fact, it is proposed that coupling A2AR antagonists with strategies aimed at bursting the levels of extracellular adenosine (by inhibiting adenosine kinase) to activate A1Rs might constitute the more robust brain neuroprotective strategy based on the adenosine neuromodulatory system. This strategy should be useful in adult animals and especially in the elderly (where brain pathologies are prevalent) but is not valid for fetus or newborns where the impact of adenosine receptors on brain damage is different

A method for validating the accuracy of NMR protein structures

We present a method that measures the accuracy of NMR protein structures. It compares random coil index [RCI] against local rigidity predicted by mathematical rigidity theory, calculated from NMR structures [FIRST], using a correlation score (which assesses secondary structure), and an RMSD score (which measures overall rigidity). We test its performance using: structures refined in explicit solvent, which are much better than unrefined structures; decoy structures generated for 89 NMR structures; and conventional predictors of accuracy such as number of restraints per residue, restraint violations, energy of structure, ensemble RMSD, Ramachandran distribution, and clashscore. Restraint violations and RMSD are poor measures of accuracy. Comparisons of NMR to crystal structures show that secondary structure is equally accurate, but crystal structures are typically too rigid in loops, whereas NMR structures are typically too floppy overall. We show that the method is a useful addition to existing measures of accuracy

The prevalence and seasonality of livestock diseases in Zaria, Nigeria:A ten-year necropsy study

A ten-year (1986-1995) record of necropsy report on diagnosed livestock diseases in Zaria, Kaduna State is evaluated to determine the prevalence and seasonal occurrence of the major livestock diseases in the Northern part of Nigetja. A total 1093 animals comprising 132 cattle, 240 goats, 318 sheep, 20 horses, 47 pigs and 336 dogs were examined at necropsy. Some diseases such as cowdriosis, Pneumonia, Ectoparasitism, and Haemonchosis showed seasonal fluctuation while others like Babesiosis, Trypanosomiasis and physical injuries were evenly distributed throughout the year. The major problem of livestock in Zaria was Pneumonia (247 cases) with a seasonal occurrence or 38.6% and 61.31% for the dry and rainy seasons respectively. During the rainy season, cowdriosis (17.42%) in cattle, Pneumonia (25.0%, 21.10% and 20.0%) in goats, sheep and horses; gastroenteritis (14.89%) and starvation/malnutrition (14.89%) in pigs and rabies (8.93%) in dogs were the major problems. Starvation/malnutrition (4.17%) in Goats and gastroenteritis (12.5%) were more prevalent during the dry season. The relevance of this report to effective control measures for the livestock resources in Nigeria is also highlighted.Key words: Prevalence, Seasonality, Diseases, necropsy, Livestock

Diseases Of Poultry In Zaria, Nigeria: A Ten Year Analysis Of Clinic Records

A to~year study of poultry diseases diagnosed at the Avian clinic of Veterinary Teaching Hospital, Ahmadu Bello University, Zaria was conducted. In all 2999 cases were studied. The commonest diseases afflicting poultry were Newcastle disease, 31.2%, Gumboro 12.0%, Ectoparasitism 7.7%, Fowl pox 6.8%, Helminthiasis 6.6% and Coccidiosis6.1%. Most outbreaks occurred in the months of May and June with the highest incidence in 1989. Fowl pox (FP), infectious bursal disease (180) and coccidiosis were more prevalent during the rainy season (May-October) while Newcastle disease (NCD) and Aspergillosis were more prevalent in the dry season (November - April). More cases of chronicrespiratory disease (CRD), helminthiasis and salmonellosis were found in poultry over 12 weeks old while gumboro, fowl pox and · coccidiosis were found more in birds less than 7 weeks old. It was concluded from this study that viral diseases (NCD, IBO, FP) ectoparasitism and helminthiasis were the most important poultry diseases in Zaria andyoung birds were more susceptible. The need for an effective poultry health programme is imperative. It is therefore recommended thateffective and uniform vaccination schedules should be conducted along with regular deworming and ectoparasite control to enhance poultry production.Keywords: Disease, Poultry, Zari

Urgent surgical repair of symptomatic Bochdalek hernia containing an intrathoracic kidney.

Bochdalek hernias rarely contain an intrathoracic kidney, and there are few reports of their operative repair. A woman presented with progressive dyspnoea limiting her quality of life. Imaging showed a Bochdalek hernia containing omentum, large bowel and the left kidney. The woman was unexpectedly admitted to the intensive care unit with respiratory failure secondary to gallstone pancreatitis whilst awaiting elective repair of her hernia. Surgical repair of the hernia was performed via laparotomy with cholecystectomy to treat both problems. The woman recovered well and is independently mobile without any exertional dyspnoea