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U.S. Import Levels Remain Strong Despite Government Shutdown
By SCMR Staff
October 08, 2013 - SCMR Editorial
October 08, 2013 - SCMR Editorial
A moderate economic recovery and a United States federal government shutdown do not appear to be enough to prevent holiday season-related import activity from posting an annual gain, according to the most recent edition of the Port Tracker report from the National Retail Federation (and maritime consultancy Hackett Associates.
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Kurt Nagle, president and CEO of the American Association of Port Authorities recently voiced his endorsement of this trade legislation
While many auto executives expect more industry recalls in 2015 and 2016, just 8 percent use advanced predictive analytics to help prevent, prepare for, and manage recalls, according to a recent online poll from Deloitte.
Purolator white paper highlights common Canadian shipping mistakes. From failing to appreciate the complexity of the customs clearance process to not realizing that Canada recognizes both French and English as its official languages, U.S. businesses frequently misjudge the complexity of shipping to the Canadian market. This often results in mistakes - mistakes that can come with hefty penalties and border clearance delays, and that can result in lingering negative perceptions among Canadian consumers.
At a certain point, it seems like the ongoing truck driver shortage cannot get any worse, right? Well, think again, because of myriad reasons we could well be in the very early innings of a game that is, and continues, to be hard to watch. That was made clear in a report issued by the American Trucking Associations (ATA), entitled "Truck Driver Analysis 2015."
Coming off of 2014, which in many ways is viewed as a banner year for freight, it appears that some tailwinds have firmly kicked in, as 2015 enters its official homestretch, according to Rosalyn Wilson, senior business analyst at Parsons, and author of the Council of Supply Chain Management Professionals (CSCMP) Annual State of Logistics (SOL) Report at last week's CSCMP Annual Conference in San Diego. The SOL report is sponsored by Penske Logistics.
Article TopicsNews · Global · Procurement · Management · Supply Chain Management ·
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Patrick Burnson, Executive Editor
Patrick Burnson is executive editor for Logistics Management and Supply Chain Management Review. Patrick covers international trade, global logistics, and supply chain management. He lives and works in San Francisco, providing readers with a Pacific Rim perspective on industry trends and forecasts. Contact Patrick Burnson


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Knik River Public Use Area Management Plan Public Review Draft
For more than a few years, residents near the Knik River and members of the public who recreate on public lands in the Knik River valley have voiced concern over the lack of direct management and law enforcement, and unlawful and dangerous activities occurring in the Knik Valley. Hearing those concerns as well as the concerns of others to continue their traditional recreational uses, legislation was passed designating the Knik River Valley and surrounding public lands as the Knik River Public Use Area (PUA) in 2006. The Alaska Department of Natural Resources (DNR) was directed through that legislation to develop a management plan for the PUA. Since then, DNR has conducted extensive land status and resource analysis and has held seven public meetings in local communities. We have also met with individuals, organizations, and with representatives of the Borough, ADF&G and several other agencies. The purpose of these meetings was to gather information necessary to develop the plan and allow the public to have feedback into the development of the plan.
Based on resource information and results of the public process, including substantial departmental review, a draft of the plan has been completed. The public is encouraged to review and comment on it. To receive full consideration and to be able to request reconsideration of a plan adopted by the commissioner, written comments must be received by 5:00pm AST, Friday, May 2, 2008.
You can request a CD containing a copy of the plan through the website or through the contact information provided below. Copies of the plan will be available at local public libraries in Palmer and Wasilla, DNR's Public Information Center at 550 W 7th Ave. in Anchorage, and at the Matanuska-Susitna Borough office at 350 E Dahlia Ave. in Palmer. A limited number of hard copies will be printed and will be available by request in the near future.
DNR will hold public hearings in Anchorage, Butte and Wasilla. The purpose of these meetings will be to present information on the PRD, provide a brief question and answer period, and provide an opportunity for the public to comment on the plan document.
The dates, locations, and times of the open house meetings are:
|March 25th
|Butte Elementary School
|March 27th
|Teeland Middle School
|March 28th
|Wendler Middle School
You can view the PRD below and provide public comments on the PRD on this website. This site provides up to date information on the planning process and management of the PUA. Through this site you may also subscribe to the contact list and view previous comments submitted during the development of the management plan.
If you would like to have your name removed from the contact list or are no longer interested in this process, please contact this office to request your name be removed.
For information related to the planning process please contact:
|Brandon McCutcheon, Plan Project Manager
|Resource Assessment and Development
|Department of Natural Resources
|550 W 7th Ave., Suite 1050
|Anchorage, AK 99501
Complete Plan (14 MB)
Preface (115 KB)
Chapter 1: Introduction and Background (145 KB)
Map 1-1: Planning Area (1.5 MB)
Map 1-2: General Land Status (1.1 MB)
Chapter 2: Goals and Management
Guidelines (175 KB)
Access (35 KB)
Commercial Use (25 KB)
Coordination (30 KB)
Facilities (25 KB)
Fees (25 KB)
Fish and Wildlife Habitat (35 KB)
Forestry (30 KB)
Health and Safety (50 KB)
Heritage/Cultural (30 KB)
Materials (30 KB)
Mitigation (20 KB)
Parcel Acquisition (30 KB)
Public Use Sites (35 KB)
Map 2-4: Wetlands (1.4 MB)
Trails (30 KB)
Waterbodies (60 KB)
Chapter 3: Management Guidelines, Recommendations, and Public Use Sites for Each Management Unit (180 KB)
Unit A – Lower Knik Flats (50 KB)
Unit B – Lakes and Wetlands (60 KB)
Unit D – Upper Jim Alpine (35 KB)
Unit E – Upper Friday Alpine (35 KB)
Unit F – Grasshopper Valley (35 KB)
Unit G – Glacier (30 KB)
Unit H – Metal Creek (60 KB)
Chapter 4: Implementation (85 KB)
Appendices (250 KB)
Map B-1: Anadromous Streams and Waterbodies (1.1 MB)
Map B-2: Waterfowl Habitat (1.2 MB)
Map B-3: Moose Habitat (1.1 MB)
Map B-4: Dall Sheep Habitat (1.2 MB)
Map E-1: Proposed Knik River Special Use Areas (800 KB)

subset: commoncrawl


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High Tea History; What is a Chocolate Pot?
If you have been to Inn Victoria's High Tea, most likely you have tried our popular fresh cucumber sandwich. What really makes this tea sandwich special is the fresh cream cheese we use from the award winning Green Mountain Farms … Continue reading


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|ASU Field Hockey Sweeps NorPac East Honors
|Written by Staff Reports
|Monday, 26 September 2011 17:28
Appalachian State field hockey senior Kelly Allaband was named NorPac East Offensive Player of the Week and freshman Dana Wetmore was named NorPac East Rookie of the Week for the second-straight week on Monday by the Northern Pacific Field Hockey Conference.
Allaband scored her first two goals of the season in the Mountaineers first win of the season. Her four points helped lead ASU to its first win at Radford in school history.
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In the press - June 2014
01 July 2014
Below are UNIT4s UK press coverage highlights from June
In with the new as Unit4 refreshes its executive team
Business software vendor UNIT4 has announced a management shake-up following its acquisition by private equity investor Advent International in a $1.6 billion deal that closed in March this year. CEO José Duarte has wielded a new broom that sweeps away the old management board structured around geographic lines and populated by decades-long company insiders. In come five new appointees from European enterprise software and services backgrounds including SAP, ATOS, Software AG and Siemens.
Duarte told diginomica yesterday that the changes had been in the works for some time: Even before the investment was made, the realignment of the top management was planned. Since we completed the transaction in mid-March we have accelerated on this. We have now pretty much the whole of the team lined up. Now its execution time. Four of the new team have been named today, filling roles heading up global strategy and operations, marketing, sales and services respectively. They will join Duarte on the management board along with Jeremy Roche, CEO of FinancialForce.com, and the companys CFO and head of HR.
A CTO has also been recruited and will be named in September, said Duarte: The organization structure changes from geographically driven to a value driven or client lifecycle chain. Im a big believer that customer centricity is key for success in any organization. Youve got to drive accountability around the customer lifecycle. Thats basically what were doing.
Read the full article here
UNIT4 begins to execute on growth strategy
Its all systems go at UNIT4 as CEO José Duarte utilises the resources available following the Advent purchase and resulting move to private company status to start executing on the goal of becoming bigger and better known. The overall strategy laid out in January is still in play, but now the resources are being visibly applied to deliver on it. One of the most obvious signs is the expansion of the executive management team. Stephan Sieber (formerly SAP) joins as executive VP for Strategy and Operations; Ivo Totev (formally Software AG) as executive VP Global Marketing; Paul Vogel (from Siemens) as executive VP Global Sales and Gonçalo Leitão (from the SAP practice at Atos and previously SAP) as executive VP Global Services.
Given their backgrounds (i.e. senior execs in much larger companies than UNIT4, and/or companies UNIT4 is winning contracts against) the appointments are a clear statement of competitive and growth intent. However, they are from very traditional companies who are working out how to operate in todays cloud-centric environment. The absence of any big names from the cloud environment is surprising, although as Duarte points out, UNIT4 can call on the expertise from its SaaS pure-play joint venture FinancialForce, and has recently appointed individuals with cloud experience in other senior management positions.
UNIT4 has made great strides in the public sector and these appointments show it intends to build on that and make similar progress in the private sector, directly and via partners. It is also recruiting a CTO (who will join the Executive Committee), whose task will be to drive SaaS business model with cloud and mobile at the fore. As Duarte says, these capabilities are pre-conditions for operating in the software market so it is not hanging back in terms of commitment (subscription sales exceeded licence sales during the last financial year .
The top level takeaway is that UNIT4 is ramping up its efforts to disrupt the enterprise software market.
One of countrys largest mental health trusts automates processing of 40,000 invoices per year
Avon and Wiltshire Mental Health Trust (AWP), one of the largest NHS trusts of its kind, has significantly streamlined its purchase-to-pay (P2P) processes with V1 document management software integrated into UNIT4 Agressos finance system. The Trust, providing large areas of the South West with mental health services and operating from more than 100 locations including prison units and hospital wings, previously relied on finance staff to manually input invoice data from the 40,000 supplier invoices received each year. AWP has now implemented V1s Capture and PDF Capture to automate the capture of invoice data from both paper and PDF invoices. This has cut the time-consuming manual capture of invoice data by up to 80 per cent and is enabling suppliers to be paid more efficiently.
As a result of implementing the V1 solution, managers, who are based across a wide geographical spread of sites, from Bath and North East Somerset, to Bristol, North Somerset, South Gloucestershire, Swindon and Wiltshire, will benefit from improved day to day management of the finance function.
Andrew Russell, Payments Group Leader for AWP, said: Before purchasing the V1 software, my team was processing invoices manually. With around 40,000 invoices a year it was particularly time consuming for staff, whereas now we have a far more automated P2P process. This is providing major cost benefits in terms of saved man hours. We chose V1s software because, being existing users of the companys BACS payment system, wed always been happy with the software and the support offered. Having gone through a competitive tending process with three other software providers, we decided that V1 was the right choice for us and the best fit with our UNIT4 Agresso finance system.
UNIT4 plots growth plans with Cloud ERP and Mobile Apps
UNIT4 is betting investments in cloud computing and mobility can raise its profile in the crowded ERP software market, following its recent move to go private. The company will also focus on becoming a top ERP (enterprise resource planning) vendor for services industries and plans to continue investing in FinancialForce.com, its joint venture with Salesforce.com, according to a statement Thursday. The company also announced a number of executive appointments. Former SAP executive Stephan Sieber has been named executive Vice President of Strategy and Operations. The company appointed Ivo Totev to the position of Vice President Global Marketing and Paul Vogel to executive Vice President of Global Sales.
Read the full article here
National Audit Office to rip out Oracle ERP system - Analyst suggests competitors like UNIT4 could be an option
ComputerWorld UK
The National Audit Office is looking to replace its existing Oracle enterprise resource planning system.
The NAO said it was inviting expressions of interest from potential bidders to provide a replacement for its existing Oracle e-Business Suite system, with additional areas of functionality like training. Through a tendering document the NAO said the five-year contract would be worth in the region of £1 million, and may be extended to cover customer relationship management. The ERP system will include accounting, financial analysis, time accounting and self-service-human resources, performance management, budgeting, payroll, e-procurement, training management and software development services.
Around 1,000 staff will need some access to the functionality. They are primarily based in the London office but around 100 staff work in the Newcastle office. Staff have the capability to work remotely via secure connections to the NAO's network. The NAO requires an annual renewal contract over five years, with a one year optional extension. The deal would include design and installation and training.
TechMarketView analyst Angela Eager said of the contract: "The NAO is no doubt acting on initiatives to generate sustainable savings, and the tender could be an attractive proposition for alternative ERP providers like UNIT4."
A problem shared
The notion of sharing has become fundamental to the UK Governments strategy to cut costs. While shared services is far from a new concept in both the public and private sectors, the past few years have seen new momentum and lateral thinking at all levels of government. The recently extended One Public Estate programme, for example, is exploring opportunities for institutions - from blue light organisations to local authorities - to slash the costs associated with their property estates by sharing offices. While in central government, the Cabinet Offices far-reaching Next Generation Shared Services (NGSS) strategy aims to achieve up to £600m of savings per year by establishing independent back-office shared service centres.
There are encouraging signs at a local level, too. Research conducted earlier this year by business software company UNIT4 found that 63% of local government managers identified shared services as a priority for reducing costs.
Read the full article here
New evidence confirms coding burden of top 4 ERP solutions
UNIT4, the global leader in software that supports business change, today released new user-based evidence collected by technology management consulting firm Eval-Source proving that its Agresso enterprise resource planning (ERP) architectural capabilities continue to provide substantial advantages for ambitious, rapidly-changing organisations, compared to other leading ERP software.
The report examines service-based organisations that consolidate to a single system and the systems ability to manage business change post-implementation for areas including governmental regulations and compliance (GRC), reorganisation and restructuring, mergers and acquisitions, business process change and financial management-driven change.
The evidence, collected from Microsoft Dynamics AX, SAP Enterprise Suite, Oracle E-Business Suite, Oracle Fusion and UNIT4 Agresso users, who each certified that they clearly understood the nature of the questions, and had faced these change situations previously, shows substantial architectural differences between the ERP offerings of the vendors.
Nobel winners say scientific discovery virtually impossible due to funding bureaucracy
Daily Telegraph
Anwen Robinson commented on article:
I am Managing Director of a business software firm that provides administration software to research organisations. In my experience talking to institutions there has been a huge increase of administration that is not limited to the peer preview process but is in addition - pre-award management, full economic costing, post award management, financial management, human resources management and more ..
In many instances this means that highly skilled researchers, and back room staff, are spending too much time on administration. Not only are potential discoveries being impacted, the situation also adds up to greater costs and time being wasted trying to find information.
There has to be a balance between enforcing quality measures and allowing innovation, finding the right mix will be difficult. Until that time however technology can help make this complex process simpler, the Universities of Oxford and Cambridge have written about simplifying the complex costing and pricing process here:
Read the full article and comments here


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Below you will find a step by step guide that should answer all your questions about Twitbin. You will find FAQs, how-to-guides, and videos. If you have questions not answered here, you can always email our support department and usually get a response within 72 hours.
Installation Instructions
Following these steps you should be able to get Twitbin running in most modern computers quickly and easily.
- Installing the plugin:
Click here to download and install the plugin from Mozilla
- Hit Accept when Firefox asks you for permissions
- Restart Firefox
- Click the bird icon up top to open Twitbin
Frequently Asked Questions
- How do I login to Twitbin?
The image below will show you the steps necessary to Authorize Twitbin to access your Twitter account. You will need to go through the OAuth steps in order to sync Twitbin with your account. This means you will also need to enter your PIN.
- How do I post a Tweet?
Click on the post a tweet field, which will expand and give you enough space to post. When you are done typing, just click send.
- How do I post a Reply (@mention)?
If you hover over the tweet you'd like to reply to, the additional controls will appear. Simply click on the reply arrow, and your new response tweet will be created.
- How do I send a Direct Message (DM)?
By right clicking on a tweet (control + click in some cases) you will load our custom contextual menu which will give you the option to create a new DM to that person. Alternatively you can click on the mail icon and be taken to your message inbox. Here there is a link where you can create a new DM. Lastly you can write in the main Twitbin posting box a message in the format of D [username] and then your message.
- How do I see my Lists?
Clicking on the following icon = will load your lists that you have created or subscribed to on twitter.com. Once in this view, you can select an individual list. Lists, just like other views will reload automatically every 3 minutes.
- How do I configure Twitbin?
Click on the gear icon in the upper right hand corner of the Twitbin interface to get to the settings menu.
- What are Twitbin Local Passwords?
We've included the option to let you locally password protect access to your twitter account. This is very useful on shared computers. This is not your Twitter password, this is a locally stored (on your machine) password which will prevent the average user from automatically logging into your stored accounts in Twitbin. We cannot recover your password for you, if you forget your password, you will need to uninstall Twitbin, and reinstall it.


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If there's one thing that working as undercover assassins and fighting terrorists in tall buildings has taught us, it's that everything worthy in life can be learned from movies. So if you're looking for love, there's nothing like sitting down with a bunch of romantic comedies and letting their sage lessons filter into your brain like music from a stereo held aloft by John Cusack.
Unfortunately, though, it's not quite that simple. When done in real life, many of the tricks used by onscreen singletons to successfully woo potential lovers can get you put away for a long time.
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Information for Transformation
This self-help alternative medicine site offers extensive educational information on the topics of natural healing, holistic and biological dentistry, herbal medicine, cleansing and detoxification, heavy metal detox, diet, nutrition, weight loss, and the finest, tried and tested health equipment and products available for the natural management of health.
Mercury, in its various forms, has a great affinity for certain minerals, as well as protein and non-protein molecules in the body. Mercurials have a great attraction to the sulfhydryls or thiols. The mercury atom or molecule will tend to bind with any molecule present that has sulfur or a sulfur-hydrogen combination in its structure. This process of combining with a metal to form a complex in which the metallic ion is sequestered and firmly bound is called chelation. A thiol is any organic compound containing a univalent radical called a sulfhydryl and identified by the symbol -SH (sulfur-hydrogen). A thiol can attract one atom of mercury in the ionized form and have it combine with itself. Because it is a radical, it can enter into or leave this combination without any change. Mercury and lead both have a great affinity for sulfur and sulfhydryls and are capable of affecting the transsulfuration pathways in the body.
The primary sulfur-containing protein amino acids in the body are cystine, cysteine, methionine, and taurine. There is also a sulfur-containing tripeptide (having three amino acids) called glutathione that is composed of glutamic acid, cysteine, and glycine. Sulfur exists in a reduced form (-SH) in cysteine and in an oxidized form (-S-S) as the double molecule cystine. Whenever mercury binds to one of these sulfur-containing molecules, it reduces the molecule's availability for normal metabolic functions.
Sulfur is present in all proteins, which makes it universally available throughout the body for binding with mercury. Some of the important biochemical sulfur-containing compounds of the body besides glutathione are insulin, prolactin, growth hormone, and vasopressin, and science has not yet investigated the effect of mercury upon them. Mercury has a particularly high affinity for thiol groups and progressively less for other groups in the following sequence: sulfur, amides, amines, carbon, and phosphate. Because of this, mercury has the potential of binding to proteins throughout the body. Mercury compounds are formed by the binding of mercury to the biological binders albumin or cysteine.
The principal biological reaction of mercury is with thiols to form mercury mercaptides. The sulfur groups are often referred to as mercaptans because of their marked affinity for mercury. Mercaptan is defined as any compound containing reduced sulfur bound to carbon. When a metal, such as mercury, replaces the hydrogen ion of the reduced sulfur, the resulting compound is called a mercaptide. Mercury can form at least three compounds with cysteine in which all or a part of the mercury is bound firmly as a mercaptide. Mercury may cause damage, especially to the placenta, by inactivation of sulfhydryl groups in cellular enzymes. Mercury interacts with sulfhydryl groups and disulfide bonds, as a result of which specific membrane transport is blocked and selective permeability of the membrane is altered. Mercury also combines readily with phosphate and heterocyclic base groups of DNA. It also combines with other ligands: amide, amine, carboxyl and phosphoryl groups.
Glutathione is Magnesium-Dependent
Glutathione protects the cells from oxidative-stress-induced apoptosis and glutathione levels are magnesium dependent! Glutathione is a very important detoxifying agent, enabling the body to get rid of undesirable toxins and pollutants. It forms a soluble compound with the toxin that can then be excreted through the urine or the gut. The liver and kidneys contain high levels of glutathione as they have the greatest exposure to toxins. The lungs are also rich in glutathione partly for the same reason. Many cancer-producing chemicals, heavy metals, drug metabolites etc. are disposed of in this way.
Glutathione (glū'tə-thī'ōn') is a polypeptide, C10H17N3O6S, of glycine, cysteine, and glutamic acid.
Glutathione synthetase requires γ-glutamyl cysteine, glycine, ATP, and magnesium ions to form glutathione. In magnesium deficiency, the ss y-glutamyltranspeptidase is lowered. There is a direct relationship between cellular magnesium, GSH/GSSG ratios, and tissue glucose metabolism. Magnesium deficiency causes glutathione loss and this is unwelcome as the clouds of radiation are touching down across the northern hemisphere. Magnesium deficiency causes glutathione loss, which is not at all healthy because glutathione helps to defend the body against damage from cigarette smoking, exposure to radiation, cancer chemotherapy, and toxins such as alcohol and just about everything else.
According to Dr. Russell Blaylock, low magnesium is associated with dramatic increases in free radical generation as well as glutathione depletion and this is vital since glutathione is one of the few antioxidant molecules known to neutralize mercury. "For every molecule of pesticide that your body detoxifies, you throw away or use up forever a molecule of glutathione, magnesium and more," says Dr. Sherry Rogers who goes on to say that, "Your body uses nutrients to make this glutathione and it uses up energy as well. Every time we detoxify a chemical, we use up, lose, throw away forever, a certain amount of nutrients."
Homocysteine is a natural substance made by the body. Homocysteine functions at a metabolic crossroad that can affect all the methyl and sulfur group metabolism of key enzymes, hormones, and vital nutrients. Many people lack the ability to break it down completely, and high homocysteine levels usually occur due to the inability to clear homocysteine because of faulty methionine pathways (mercury and lead toxicity). The result is a buildup of homocysteine in the system. When it is not completely broken down, homocysteine becomes a very dangerous substance that can exert harmful effects and increase disease-causing oxidation. When it is broken down completely, it can furnish necessary substances for other beneficial reactions in the body (methyl and sulfur groups). These necessary substances provide the fuel for vital processes like liver detoxification, adrenal gland support, neurotransmitter synthesis, and joint cartilage and bone regeneration. Homocysteine is a very dangerous substance that is harmful to the arteries, which makes it a risk factor for heart disease if it is not broken down completely.
Homocysteine can cause clotting, increase harmful oxidation, and can injure the blood vessel wall (especially if already weakened by x-rays), allowing cholesterol and fat to infiltrate into the wall and cause what is known as a foam cell. This foam cell swells and protrudes into the space of the artery and obstructs the blood flow, potentially resulting in a heart attack. The artery is usually damaged and cholesterol is oxidized before infiltration into an artery and creation of a foam cell can occur, and homocysteine can damage the artery, oxidize the cholesterol, and decrease circulation, all of which increase the risk of heart disease.
The first correlation between homocysteine and disease involved cardiovascular disease, but since then, toxic effects have been revealed on other organ systems, including the liver, adrenals, joints, nerves, and general system blood vessels (inclusive of placental tearing). Neuropsychiatric conditions have also been traced to homocysteine problems, and a correctly functioning pathway is vital to neurotransmitter synthesis. Other conditions which have been linked to high homocysteine levels include neural tube defects, multiple sclerosis, rheumatoid arthritis, spontaneous abortion, placental abruption, renal failure, osteoporosis, and type II diabetes.
Homocysteine is not toxic when the pathway is functioning properly. Synergistic nutrients facilitate the homocysteine pathway, preventing toxic levels of homocysteine from accumulating, and make it possible for a functioning pathway to provide necessary methyl groups and sulfur groups for a myriad of biochemical reactions, especially those needed for detoxification and joint and cartilage repair. Nutrients which facilitate the methionine pathway and reduce homocysteine include betaine, dimethylglycine, and vitamins B6, B12, folic acid, niacinamide, choline, betaine, dimethylglycine, magnesium, and molybdenum. Homocysteine is recycled to methionine in the presence of B12, folic acid, and methyl donors such as choline or betaine (trimethylglycine). B6 (pyridoxyl-5-phosphate is the active form) and magnesium help convert homocysteine to cysteine. Molybdenum is an essential trace mineral necessary to convert the toxic sulfite molecule to the important sulfate molecule needed for many biochemical reactions.
Niacinamide, a B vitamin, can increase the activity of two crucial enzymes needed to facilitate conversion of homocysteine to non-toxic substances. Niacinamide is also necessary for steroid hormone synthesis (cortisol, estrogen, progesterone, testosterone, DHEA), and when chronic stress on the adrenals favors cortisol production, a limitation in niacinamide and/or precursors allows cortisol to be made at the expense of other steroid hormones (such as DHEA). This results in increasingly large ratios of cortisol to DHEA, leading to tissue insensitivity to insulin. All the excess cortisol will need to be conjugated (detoxed in the liver), and this happens largely through sulfur-dependent detoxification pathways in the liver. For this, the homocysteine path has to be functioning to provide the sulfur groups for liver detoxification. Providing these sulfur groups can take some of the stress off the adrenals when cortisol is excessive. Zinc, selenium and magnesium are all minerals which are important co-factors in enzyme reactions of the homocysteine pathway. Zinc and selenium are co-factors for antioxidant enzymes. Magnesium is needed to convert methionine to SAM (S-adenosylmethionine) for the end reaction which converts the toxic sulfite to the essential sulfate, and for glucose metabolism (glucose is a substrate for glucuronic acid, hyaluronic acid, N-acetyl-glucosamine, and chondroitin sulfate--all building blocks for cartilage and joint repair). Chronic mercury inhalation from mercury fillings, with its great affinity to bind to methionine and cysteine can decrease the availability of these amino acids and affect the metabolism of both vitamin B12 and folic acid.
Mercury can inhibit or modify how the body uses ATP, zinc, selenium, rubidium, vitamins A and C, and calcium. Cancer cells have altered sodium and calcium transport and reduced oxygen transport through the cell membrane. The oxygen deficiency within the cell reduces or eliminates the ability of the cell to oxidize glucose to carbon dioxide, which in turn, results in the conversion of glucose to lactic acid, lowering cellular pH into the acid range. These combined effects radically change cell metabolism and ultimately DNA replication. Mercury can alter sodium and calcium transport and also reduce the amount of oxygen transported. Mercury competes with calcium for cellular binding sites and, through this mechanism, can decrease cellular calcium or increase extracellular calcium. Mercury binds avidly to rubidium and selenium. Decreases in available selenium can also reduce available GSH-Px (glutathione peroxidase), which, in turn, causes a proliferation of free radical cellular damage. Mercury, at extremely low levels, can inhibit the respiratory burst of killer-cell leukocytes, reducing their effectiveness in controlling cancer cell proliferation.
A healthy redox balance depends on a fluid shift between glutathione synthesis and methylation, especially when responding to environmental toxins, stressors, or infections. Two B vitamins, folate and cobalamin (B12), are absolutely essential for this fluid, dynamic shift. Most important, the body must be able to adequately convert both nutrients to their active forms, so they can do their job in helping the body methylate when needed, and make more glutathione when needed.
Methyfolate is the only substance that can donate a methyl group to B12, making the all-important and highly active methylcobalamin.
Folate occurs naturally in many foods. Foods high in folate include leafy green vegetables (such as spinach, chard, turnip greens, romaine, broccoli), citrus fruits and papaya, cantaloupe, pineapple, honeydew and bananas, eggs, beans, peas, as well as beef liver. Different forms of folate—before its conversion to methylfolate—play many important roles in the body. They help regulate the healthy growth of new cells, which is especially important for an embryo and newborn. They are necessary to make both DNA and RNA, and help protect DNA from mutations that might lead to cancer.
They are crucial to making normal red blood cells (they help form heme, the iron-containing protein in hemoglobin), and it is essential for metabolizing homocysteine so that this amino acid doesn't build up to unhealthy levels. Because folate is so important, the Food and Drug Administration published regulations in 1996 requiring that the synthetic form of folate, called folic acid, be added to breads, cereals, flours, pastas, rice and other grain products so commonly eaten by Americans. This helped prevent birth defects and miscarriage, since folate is needed during pregnancy and early life. Thus today, grains are also a source of the synthetic form of folate, folic acid.
Though folic acid is stable and has a long shelf life, the body must convert it into folate in order to use it. Studies show transformation of folic acid falls off after ingesting 200 mcg, and is saturated around 400 mcg. When it is not converted, it can remain in the bloodstream for days, even weeks at a time. In addition, there is some conflicting evidence that high-dose supplementation of folic acid may contribute to risk of certain cancers.
On the other hand, dietary folate seemed protective, although not at a rate that was statistically significant. The researchers conclude: "These findings highlight the potential complex role of folate in prostate cancer and the possibly different effects of folic acid-containing supplements vs. natural sources of folate." However, one issue they sidestep is whether a synthetic supplement, folic acid, that has to be converted back to folate, may itself cause problems.
Genetic variations mean that some of us have trouble converting B12 to the active forms.
Although the body has many uses for folate, one is to serve as a building block for methylfolate. Methylfolate is the only substance than can donate a methyl group to B12, making the all-important and highly active methylcobalamin. Because of genetic variation, some people are less efficient at conversion, and when their bodies are stressed they may not make enough methylfolate. Then their ability to methylate and to make glutathione will be impaired, contributing to many chronic health problems. Testing can help determine if conversion capacity is low. Supplements of methylfolate are available, in a calcium salt form of 5-methyltetrahydrofolate, and in a newly available form, a glucosamine salt of 5-methyltetrahydrofolate, which has demonstrated greater solubility and bioavailability in preliminary studies. The new 5-MTHF glucosamine salt was shown to be approximately 100 times more soluble and increased plasma levels 20% higher in rats and 10% higher in humans than the calcium salt form.
Cobalamin, or B12, is a very interesting vitamin, which actually contains the mineral cobalt, giving it that lovely, striking red color. In 1934, three researchers won the Nobel Prize for the discovery that eating large amounts of raw liver, which contains high amounts of vitamin B12, could save the life of incurable patients with fatal pernicious anemia. This finding saves 10,000 lives in America each year. The vitamin itself was isolated from liver extract in 1948 and its structure was characterized 7 years later.
Deficiency of vitamin B12 impairs DNA synthesis, affecting the growth and repair of all cells. Everything from anemia to neuropathy, weakness, loss of appetite or taste and smell, irritability, memory impairment, tingling and numbness can be symptoms of Vitamin B12 deficiency.
B12 can be converted by the body to an active form known as adenosylcobalamin. This form interacts with the enzyme methylmalonyl CoA mutase and is used by the mitochondria, the energy powerhouse of the cell. Vitamin B12 can also be converted to another active form, methylcobalamin. Methycobalamin is a cofactor for the enzyme methionine synthase, and is a key nutrient in both methylation and in regulating the synthesis of glutathione. As with folic acid, supplements of B12 are often available in a synthetic form called cyanocobalamin, which has a long shelf life, but must be converted by the body back into a useable form. In addition, the body's ability to absorb B12 from typical oral dietary supplements is limited by the capacity of something called intrinsic factor, a glycoprotein secreted by the stomach. Only about 10 mcg of a 500 mcg oral supplement is absorbed by healthy people, simply because it exceeds the ability of available intrinsic factor.
We cannot make our own B12. Bacteria in our gut can make it for us and other mammals. Naturally occurring B12 is found in animal products, including fish, meat, poultry, eggs, milk, and milk products. Vitamin B12 is generally not present in plant foods, but like folic acid, certain foods such as breakfast cereals are fortified with it in a cyanocobalamin form. As we age, we can have more difficulty absorbing B12 from food. In fact, many of us may be deficient in B12.
Genetic variations mean that some of us have trouble converting B12 to the active forms. Urine tests can reveal deficiencies of the active forms even when blood tests show adequate B12.
Surprising new research demonstrates that diabetic neuropathy, an extremely painful condition, may respond to supplementation with the active forms of three b vitamins: methyl B12, methylfolate, and the active form of vitamin B6 (pyridoxal-5'-phosphate). Major depression responded to methyfolate in combination with antidepressants in a 2011 study.
Methylfolate alone may sometimes be useful in clinical depression. A 2009 report and review from Harvard Medical school notes that folate is needed for the synthesis of norepinephrine, serotonin and dopamine.
Another 2011 study finds that methyl B12 rescues neurons from homocysteine-mediated cell death. Excess homocysteine is known to be toxic to neurons and can initiate cell death. Methyl B12 was able to reduce levels of an enzyme, caspase, involved in cell death. The researchers concluded that methyl B12 might be useful in treatment of late stage ALS, since homocysteine levels have been found to be increased in animal models of the disease.
Autism also responds to treatment with methycobalamin. The researchers report that there were "significant increases in cysteine, cysteinylglycine and glutathione … the oxidized disulfide form of glutathione was decreased...targeted nutritional intervention with methylcobalamin and folinic acid may be of clinical benefit in some children who have autism."
In the simplest terms, maintaining life can be viewed as the ability to resist oxidation. Oxygen is essential to life, but oxygen is like fire. It can be very damaging and needs to be controlled by antioxidants, known as "reducing" molecules. Balancing reduction and oxidation—or redox—is the fundamental challenge of life. What's great about that word, redox, is that it shows that they are profoundly linked and we need both. Once you understand this relationship, it leads to all kinds of new insights.
From the very moment of conception, life can be sparked by the unique redox environment created when a sperm fertilizes an egg. The sperm is extremely rich in proteins containing the mineral selenium, which is a potent reducing agent for glutathione, the most important antioxidant molecule in cells. The egg, on the other hand, is very rich in glutathione. Bring these two potent antioxidant strategies together, and you create an exceptionally reduced cell that can initiate life and promote development using the power of redox. That reducing power provides a metabolic spark as new life begins its journey, allowing the rapidly dividing cells to safely maintain a high rate of oxidation. The same metabolic challenge continues as the embryo develops. The entire nervous system and the shaping of gene activity are profoundly influenced by this redox balance as well. Aging is essentially a process of gradual oxidation, and our health as we age depends on successfully quenching that oxidation. Finally, innumerable diseases are linked to high levels of oxidation and low levels of glutathione—from schizophrenia to major depression, autism, chronic fatigue syndrome, fibromyalgia, and most chronic autoimmune and chronic inflammatory diseases.
Glutathione is made from cysteine, glycine, and glutamic acid. You can get cysteine from the diet, in meat, eggs, garlic, onions, red pepper, broccoli and other foods. Cells in the gut lining, aided by transporter molecules, will bring it into the body. Both gluten (found in grains such as wheat) and casein (milk protein) can inhibit the uptake of cysteine, which the body needs to make glutathione. So many children with autism, or adults with autoimmune disorders, do better when they eliminate wheat and milk from their diet. It's due to a redox mechanism.
Both casein and gluten are broken down into certain peptides that are relatively stable. The protein casein is broken into casomorphins. The "morphins" are so named because, like morphine, they act on the opiate receptors. The most famous one, beta casomorphin 7 (BCM7), has seven amino acids. Our recent research shows that BCM7 first stimulates the uptake of cysteine, but then inhibits it. However, the human BCM7 is markedly different than bovine BCM7 from the cow. It turns out that the BCM7 from a cow inhibits cysteine at least twice as much as the BCM7 from a human mother. The implications for health are profound if you start thinking about formula feeding and all the dairy products from cows in our diet. Breastfeeding is clearly regulating the redox system of newborns. A diet high in dairy from cows can promote a decrease in our antioxidant capacity, our ability to make enough glutathione.
The peptide from sheep's milk behaves more like human milk. Similarly, the protein in gluten is known as gliadin, and it also creates a seven amino acid peptide, like BCM7. We already know that gliadin can trigger celiac disease, and can also lead to gluten intolerance and sensitivity. These problems reflect the ability of gluten peptides to inhibit cysteine uptake, perhaps contributing to chronic inflammation, although we have more to learn about that. Of course, not everybody who eats diary or wheat has poor antioxidant capacity, and milk and wheat are important sources of nutrition. There are probably genetic vulnerabilities that bring some people closer to a critical point for oxidative stress, while for others it is a non-issue. Overall, though, this is an issue to consider in any chronic inflammatory disease or neuro-immune disease.
Methylation and glutathione are very tightly intertwined. There is a critical metabolic intersection—a fork in the road—where cells must decide to either make more glutathione, or support more methylation. The overall balance between these two options is crucial to health.
Your body can take homocysteine and convert it back to cysteine. Homocysteine is a metabolite of the essential amino acid methionine, and elevated levels have been associated with vascular disease. Homocysteine is created when methionine donates its methyl group to another molecule in a process known as methylation.
Methylation is a fundamental process of life which is intimately linked to redox status. In chemistry, a methyl group is a hydrocarbon molecule, or CH3. When a substance is methylated, it means that a CH3 molecule has been added to it. Methylation can regulate gene expression, protein function, even RNA metabolism. It can suppress viruses, even latent viruses or cancer viruses we are born with and can help us handle heavy metals. In the liver in particular, methylating a toxin helps change it to a form of the compound that can be more easily processed and excreted.
Methylation is an extremely broad and fundamental action that nature uses to regulate all kinds of processes. It regulates epigenetic changes—changes to gene expression that occur because of environmental factors—by affecting how DNA unravels during development. Some changes can be permanent for the whole lifespan and can even be passed down as many as three generations. That shows that the environment, through the process of methylation, can be quite a profound influence. There are 150-200 methyl transferase enzymes, and each enzyme can methylate multiple targets. So you can imagine methylation as a spider's web within each cell, and that web branches out in many directions.
Methylation and glutathione are very tightly intertwined. There is a critical metabolic intersection—a fork in the road—where cells must decide to either make more glutathione, or support more methylation. The overall balance between these two options is crucial to health, and this occurs with homocysteine. When methionine gives away its methyl group, we're left with homocysteine. And the body has to decide, should homocysteine be methylated, and go back into methionine, or should it be converted into cysteine, so that the body can make more of the antioxidant glutathione? This fundamental decision is made again and again by the body, and the overall balance is crucial to health. Too little glutathione and we will end up with free radical, oxidative damage. Not enough methylation, and many genes and viruses will not be properly regulated. Excess homocysteine, and the risk of vascular disease goes up.
It's important to understand that multiple factors impinge on the same system. What's so important here is that the glutathione antioxidant system is a common target for so many different environmental toxins and infections. Every single one of them impinges on the glutathione system. It's not that each molecule of mercury or lead picks off one glutathione molecule. No. It's that in general, environmental assaults inhibit the enzymes that are responsible for keeping the glutathione in its reduced antioxidant state, where it can do its job. The potent ability of mercury to inhibit selenium-containing enzymes is a good example.
Some people sail through these stressors and remain healthy, while others stumble and fall. Though many molecules and nutrients are important, the active forms of vitamin B12 (adenosylB12 and methylB12) and the active form of folate (methylfolate) are essential to this process. Once you have the raw material to make glutathione or to methylate, you need cofactors like methylfolate and methyl B12 to complete the process. If we don't make enough of these active forms, we will not be able to smoothly and fluidly shift between methylation and glutathione.
Nature allows, and even encourages, genetic variation, and the bottom line is that some people have genetic variations that render this process less functional. Even with a less functional genetic legacy, you might be fine if you are not stressed by the environment—in particular by chronic infections or toxic assaults. Stress brings out limitations in genes that otherwise are latent and not problematic. That's a general truth. So yes, with proper testing by a doctor to see if there is a functional deficiency, supplementation with active forms can help. For example, there is a test that measures levels of methylmalonic acid (MMA) in the urine; if the levels are high, you are not making enough of the two active forms of B12. Your serum B12 may be perfectly normal—you just aren't converting enough of it to the active form.
We ourselves cannot make B12, also known as cobalamin. Bacteria make it for us, and since vegetables don't carry those bacteria, vegans can be deficient in B12. B12 is such a precious material for the body that if, for instance, you eat a piece of rib eye steak, the B12 released from the proteins is instantly bound right there in the GI tract and chaperoned as if in a football handoff to be carried to cells, transported inside and then processed into the two active forms. Nature knows this is a precious material for life, and a critical indicator of cellular oxidation status.
There are several natural forms of B12 which need to be converted into the active forms, adenosylB12 and methylB12. CyanoB12, the form in most vitamin supplements, is not active and is less useful than the active forms for treating deficiency states. Glutathione itself is needed for converting other forms of B12 to the active forms. Indeed, there is a type of cobalamin called glutathionylcobalamin that is an intermediate for making the active forms.
There are two enzymes in the human body that require active B12 as a cofactor. One is called methylmalonyl CoA mutase, and it needs adenosylB12. It is an enzyme that is necessary for the mitochondria—the energy powerhouse of your cell—to function. The other enzyme that requires active B12 is the enzyme methionine synthase, which requires methyl B12.
MethylB12 is constantly recycled. It donates its methyl group to homocysteine, which then turns into methionine. Once B12 is missing its methyl group, it needs to get a fresh one. And that's where methylfolate comes in. Methylfolate is in essence a methyl donor for methionine synthase. That's its job in life. It is the only molecule than can donate a methyl group to B12. Once it does that, the rest of the folate is available to go out and support all kinds of other reactions in the body that need plain folate.
When your level of methylB12 is low, homocysteine builds up and this can have adverse health effects. High homocysteine levels in the blood reflect low activity of the enzyme methionine synthase, and this has been linked to an increased risk of atherosclerosis and coronary artery disease. It is also well known that homocysteine levels are increased in Alzheimer's disease, which suggests a role for impaired methylation in this neurodegenerative disorder. Of course low B12 levels are classically associated with pernicious anemia and with peripheral neuropathy.
Low levels of folate are also classically associated with anemia, heart disease, fetal abnormalities such as spina bifida, as well as neuropathies and these have been specifically linked to a deficiency in methylfolate. In addition, recognition of the important role of methylfolate and vitamin B12 in supporting D4 dopamine receptor methylation links their deficiency to impaired attention such as attention-deficit hyperactivity disorder (ADHD). People with genetic polymorphisms in the enzyme that makes methylfolate are particularly vulnerable to a deficiency.
Some research has shown that synthetic folic acid can build up when supplemented, and a few studies have suggested this may even be linked to cancer in high doses.
In addition to vitamin B12 and methylfolate, there are several other nutritional supplements whose actions are critical for redox and methylation pathways. Vitamin B6 (pyridoxal-5-phosphate or P5P) is an essential cofactor for the two enzymes that sequentially convert homocysteine to cysteine, namely cystathionine-beta-synthase and cystathionine-gamma-lyase. Together these two B6-dependent enzymes comprise the transsulfuration pathway that promotes glutathione synthesis. The common supplement form of vitamin B6, pyridoxine, must be converted to the active form, and in some disorders, such as autism, this conversion is impaired, so the P5P form may be more effective. N-acetylcysteine (NAC) provides a supplementary source of cysteine. NAC can cross into the cell cytoplasm where the cysteine is released and allowed to promote glutathione synthesis. SAMe is an active, methyl-donating derivative of the essential amino acid methionine, and during oxidative conditions its levels may be low, due to low methionine synthase activity. SAMe has shown particular benefit in treating depression.
These examples of the interrelationship between oxidation and methylation are just the tip of the redox iceberg. Nature has learned to harness the power of oxidation as a signaling mechanism to control cellular activity. When more antioxidant is made available, cells can safely undertake a higher level of metabolic activity. There is a lot more to learn, and the real challenge will be to convert this evolving knowledge about redox and methylation into new, more effective treatment strategies.
Cysteine (sis-tee-in) is a unique amino acid, largely by virtue of its sulfhydryl group. It is an important constituent of proteins, being largely responsible for their molecular configuration, either by forming disulfide bonds with other cysteine molecules incorporated into the same protein or by forming disulfide bonds with free cysteine. It can link together a number of separate proteins or polypeptides by forming disulfide bonds between cysteine residues in different molecules. Cysteine is made from two other amino acids, methionine and serine. Methionine furnishes the sulfur atom and serine furnishes the carbon skeleton in the synthesis of cysteine. Cysteine is produced by enzymatic or acid hydrolysis of proteins. Cysteine can be oxidized to cystine (sis-tin), which is rather insoluble in water. Sometimes it can be found in the urine and in the bladder in a crystal form where it will form cystine calculus (stones) in the kidneys or bladder. Cystine is the main sulfur-containing compound of the protein molecule. Upon reduction, cystine produces two molecules of cysteine. Heavy metals catalyze the oxidation of cysteine to cystine and also react with cysteine to form mercaptides. Cysteine is very soluble in water and therefore can be easily eliminated via the urine.
However, cysteine can be oxidized to cystine, which can then present the potential of stone problems. If an adequate supply of vitamin C is available, it will help keep cysteine in its reduced and soluble form, thereby preventing the formation of stones. The ratio of vitamin C to cysteine should be three-to-one. Cystathionase, an enzyme that is necessary to change cystathionine into cysteine, and which is present in humans postnatally, is not present in human fetal liver or brain. Cysteine is not considered an essential amino acid in adults. Cysteine is an essential amino acid for the human fetus, and for prematurely born and full term infants for a short period after birth. Its concentration in maternal plasma is greater than or equal to that in fetal plasma. Cystathionine, which is present in human brain in large concentrations, may not be needed until some time after birth.
Methionine is one of the essential amino acids required in the diet, whereas cysteine is considered to be non-essential. Eighty to 90% of the daily requirement can be replaced by cystine. The ability for one sulfur to replace another is called transsulfuration and represents an important route for either cysteine or cystine. Plasma levels of taurine, serine, methionine, and threonine have been found to be significantly lower in patients with essential hypertension (high blood pressure). The levels of these four amino acids, as well as total sulfur amino acids, correlated inversely with systolic blood pressure. Individuals with mercury amalgam dental fillings could have low plasma sulfur amino acids, leading to high blood pressure. Mercury has been shown to affect methionine use.
Taurine is a sulfur-containing amino acid that the body makes from cysteine. Methionine is a precursor for cysteine and taurine biosynthesis. There are two primary bile acids needed to break down fats; one of them, taurocholic acid, cannot be produced without taurine. Taurine is concentrated in the brain where it functions as a neurotransmitter and/or as a modulator of neurotransmission, preventing excess electrical activity, such as that occurring during epileptic episodes. Taurine plays a major role in the transport regulation of blood electrolytes (calcium and potassium) and may affect in the cardiovascular system. Excretion in pregnant women falls dramatically starting at week-9 of pregnancy. Reserves of taurine are increased for use during the latter phases of pregnancy. Concentrations are higher in the fetal liver and brain and some believe that it plays a role in brain development and also functions as a growth modulator. Both mercury and lead have a great affinity for the sulfur atom. Mercury can serously interfere in the transsulfuration pathway at many different locations, ultimately leading to a deficiency or reduction in available taurine.
Glutathione is present in almost all cells in the body in rather high concentrations. Glutathione serves as a storage and transport form of cysteine and also as a respiratory carrier of oxygen, both extremely important metabolic functions. Within the cell itself, it has some very important metabolic functions such as protecting the cells against damage that can be caused by free radicals and hydrogen peroxide. In the liver, glutathione is a reservoir of cysteine which is utilized for protein synthesis. Glutathione can also replace cysteine derived from methionine, thus exerting a methionine sparing action. Vitamins C and E are two key nutrients that go through this recycling process. Once they have performed their function as an antioxidant, scavenging free radicals, they are reduced to an inactive state and must be regenerated to their original form. This process requires an adequate supply of reduced glutathione. Reduced glutathione (GSH) is present in red blood cells where it is functionally associated with the enzyme glucose-6-phosphate dehydrogenase (G6PD) and the coenzyme reduced nicotinamide-adenine dinucleotide phosphate (NADPH). Both G6PD and NADPH are needed to maintain red blood cell integrity.
Glutathione also plays a part in how our immune systems function. When the supply of glutathione is low, or has been depleted, this can inhibit the activation of lymphocytes, and may also have a bearing on the response of cytotoxic T-lymphocytes. The ability of mercury to affect the available supply of glutathione also affects these same lymphocyte functions. Mercury also inactivates G6PD, which results in altered red blood cell membrane permeability and blocking of active glucose transport into cells. Mercury itself increases red blood cell membrane permeability. The altered membrane permeability, in turn, disrupts a large number of essential membrane functions, ultimately leading to cell death. Glutathione peroxidase (GSH-Px) activity in the liver, kidneys, testes, and erythrocytes is significantly depressed by silver and mercuric chloride.
The antioxidant glutathione, known as GSH, is arguably the most important antioxidant the body makes, and most certainly the most powerful intracellular antioxidant. In its reduced form it plays a pivotal role in DNA repair, immunity, flushing of toxins, removal of heavy metals, quenching of free radicals, and recycling of other antioxidants such as vitamins C and E. Glutathione supports detoxification in the lining fluid of the lung and intestines, enhances macrophage function, and slows virus production.
Low levels of glutathione are associated with an astonishing range of diseases, from diabetes to Parkinson's to asthma to kidney problems, and many other conditions. Unfortunately, oral supplementation of glutathione has proven tricky and sometimes ineffective, since the molecule, when taken orally, is not able to effectively reach and be absorbed into the intracellular space where it is needed. Optimal exposure to the potential benefits linked to GSH have been achieved with IV therapy but it is expensive and inconvenient, and has only short-term benefits, and so needs to be repeated frequently.
The contribution of GSH deficiency in many pathologies has stimulated a number of researchers to find new potential approaches for maintaining or restoring GSH levels. One novel formulation of the molecule, S-acetylglutathione (S-GSH), is surprisingly well absorbed by cells and of great potential benefit. It crosses the cell membrane more easily than GSH itself, and is easily de-acetylated in the cell, becoming active GSH. S-GSH can be effectively absorbed by cells after an oral dose and has great potential in comparison to IV therapy.
S-GSH proved a significant anti-viral agent both in vitro and in animal studies in a 2005 study from Johann Wolfgang Goethe University Hospital in Germany. Remarkably, it was stable in plasma and taken up directly by cells with subsequent conversion to GSH (the active, reduced form). In cell culture, S-GSH efficiently restored intracellular glutathione, and in mice, S-GSH but not plain glutathione, significantly decreased virally induced mortality. This novel form of glutathione was active and stable.
S-GSH has also been shown to cause the death of certain cancer cells. In a study in the International Journal of Oncology, S-GSH induced significant cell death in three human lymphoma cell lines. It did not have the same effect on normal lymphocytes. The researchers concluded that "S-acetyl glutathione specifically activates programmed cell death in lymphoma cells." In fact, their analysis showed that this form of glutathione depleted intracellular glutathione in the cancer cells, in a selective effect that was the opposite of its action in normal cells.
Finally, in mice infected with a viral complex, S-GSH was able to reduce spleen viral content by 70% and lymph node viral content by 30%--and to do so at half the concentration of GSH. As the Italian researchers note in Molecules, glutathione analogues such as S-GSH "may offer a promising therapeutic alternative for reducing the GSH functional loss related to many human diseases."
Glutathione peroxidase protects the human brain. When polyunsaturated fatty acids, which are located primarily in the brain, are oxidized, organic hydroperoxides are formed that can only be reduced by GSH-Px. Alterations in GSH-Px activity and tissue damage caused by peroxide accumulation is of significance in the development of senility and degenerative neurological diseases. One of the primary ways the body gets rid of metal compounds is through a pathway that goes from the liver into the bile where they are then transported to the small intestine and excreted in the feces. Inorganic mercury is complexed with glutathione in the bile, suggesting that glutathione status is a major consideration in the biliary secretion of mercury. This same pathway is affected by a mercury induced reduction of available taurine needed to produce bile acid (taurocholic acid).
When the microflora of the intestine have been reduced through stress, poor diet, use of antibiotics and other drugs, fecal content of mercury is greatly reduced. Instead of being excreted in the feces, the mercury gets recirculated back to the liver. The person who is under stress, eating a poor diet, and/or taking antibiotics will tend to maintain a higher body burden of mercury derived from dietary sources--especially if they are eating fish.


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Jackson County
Man reporting a personal-injury wreck involving a white vehicle that left the road, Interstate 65 at the 39½-mile marker, Crothersville, 7:19 p.m. Tuesday.
Caller reporting someone shot her dog with a high-powered rifle, 4000 block of North County Road 460W, Freetown, 5:19 p.m. Tuesday.
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A D.C. disaster so big, it takes the Trifecta lads three videos to document the mess.
Student Loan Interest Rates to Go Up After Negotiations Fall Through
Last year's threatened July 1 hike was a central campaign-trail topic for President Obama.
Wrestling Over Food Stamps Dooms Farm Bill
Conservative lawmaker: "The farm bill died because the Democratic leadership had indicated they wanted it to die."
Senate Dems' Effort to Move to Budget Conference Blocked for 15th Time
Cruz won't take a deal to keep debt ceiling out of budget negotiations.
About That Leverage We Had Over Ecuador in Snowden Case… Never Mind
Obama urged "to send a clear message to Correa that his ill-considered actions will not go without consequences" as Correa calls off trade deal, offers us human-rights training grant.
PJTV's ZoNation: Lil' Wayne Is a Flag Stomping Coward (Video)
Hear what AlfonZo Rachel thinks of the Lil' Wayne flag stomping controversy. Did Lil' Wayne make a mistake, or did he really intend to trample on the stars and stripes?
For some better music, listen to Zo's band, 20 Lb. Sledge. Find more info at www.Facebook.com/20lbSLEDGE.
PJTV subscribers, click here to catch all of Zo's videos; for an embeddable YouTube version of the above clip, click here.
Vladimir Putin Survives Worst Month of His Reign
Without legitimate U.S. pressure, Putin remains safely in control.
Failure Deniers: Climate Change and Public-Sector Science
If not taxpayer-funded, the massive failure of warmism advocates would have been addressed long ago.
Senate Sends Immigration Reform to House with 14 GOP Votes
Opponent Jeff Sessions called the bill, which passed 68-32, "a surrender to lawlessness" and warned that it will "decimate immigration enforcement."
Obama's Proxy War on Mideast Christians
Even if Obama really were Muslim, what more could he possibly do to empower Islam?
Who Else Has Slipped Through the Security-Clearance Cracks?
Senators warned that there is an "alarmingly insufficient level of oversight" of OPM's Federal Investigative Service.
Obama Executive Order Creates Native American Affairs Council
Right after administration tries to evade court-ordered payments to tribes and before half a million Indians are expected to face ObamaCare penalties.
Blowing Smoke: Obama Climate Speech Riddled With Lies
A dangerous, arrogant, fact-free tirade.
Why Snowden Picked Ecuador
The NSA leaker knows that President Rafael Correa wants to be the next Hugo Chávez.
Norquist to PJM: 'Robust Guest-Worker Program' More Important Than 'Big Wall'
"Immigration is what's made us economically strong, politically strong, militarily strong, culturally cohesive and strong."
Obama's Falling Numbers No Panacea for Conservatives
His approval ratings will not stop his agenda. Also read: Fox News Poll: Obama In Free-Fall
Obama Barrels Ahead: Climate Plan Won't 'Pause for Partisan Gridlock'
McConnell: "Declaring a 'War on Coal' is tantamount to declaring a war on jobs."
Jarrett Keynotes Pentagon's Gay Pride Event, Touting Obama's 'Most Significant Civil-Rights Accomplishment'
Similar gay-pride events were being held at other U.S. installations including Kandahar and Bagram air bases in Afghanistan.
Snowden Snowballs Into Colossal Embarrassment for Obama and his Foreign Policy
Negotiated whats? Russia and China all too happy to show the world that they hold the cards, not Washington.
Corker-Hoeven Clears Procedural Hurdle as Immigration Bill Hurtles Forward
The 67-27 cloture vote indicated the final bill could see smooth sailing to passage before the July 4 break.
Hot Topic: What Is the Biggest Scandal Facing the Obama Administration?
Former Nixon White House aide Dwight Chapin has an opinion. What's yours?
The Backwards Trial: A George Zimmerman Prosecution Primer
The bizarre trial, in which the prosecution must impeach the police investigation, begins.
Of Moderates and Mu'tazilites: How Islam Wins
It's high time we awakened from the dream that Islamic moderates will save the day.
U.S. Partnership Tries to Tamp Down Stubborn Violence in Mexico
Over 40 percent of Mexicans reported that they or a family member had been a victim of a crime in the past year.
Rep. King: 'If We See Them Pass Amnesty, It's Amnesty Forever'
Iowa lawmaker rallies conservative members to oppose immigration reform bill.


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Bella's wedding look...without the dress.
Photo: Courtesy of Summit Entertainment
Some may say Will and Kate were the wedding event of the century, but that's clearly hyperbole. The real wedding we are holding onto our hankies for doesn't even exist, and that is the one between Twilights' Edward and Bella. Duh. The internet has been a hot, hungry cesspool of speculation, and the Twilight crew has been doing an absolutely wonderful job of feeding our appetite without giving anything too revealing away. Which is actually great—we want to be surprised, but our shock and awww (GET IT? PUNZ.) won't diminish if we know just a few deets, right? Like, maybe Kristen Stewart needing to cover up with a Volturi cape every time filming was paused like she was some sort of vampire captive?


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October 26, 2013
Mary Lynn Veach Sadler Biography
Mary Lynn Veach Sadler
(Dr.) Lynn Veach Sadler grew up in the Friendship community near Warsaw (Duplin County), North Carolina, where her family still runs Veach Lumber Company. She attended Warsaw schools through her junior year and was graduated from Sanford Central High School as Co-Valedictorian. Her husband, Dr. Emory Sadler, a psychologist, is a native of Kenansville (also in Duplin County). They have traveled around the world five times, with Lynn writing all the way.
Formerly a college president in Vermont, Lynn has a B.A. (Magna Cum Laude, Honors, Phi Beta Kappa) from Duke and an M.A. and a Ph.D. (Phi Kappa Phi) from the University of Illinois. Her postdoctoral study includes Milton at UCLA and the Clark Library, a certificate in administration from Bryn Mawr College and Higher Education Resource Services, and Tudor-Stuart history at Balliol College, Oxford, through the University of Alabama. She taught at Agnes Scott College, Drake University, and A&T State University and was Director of the Division of Humanities at Bennett College, where she set up what is thought to be the first microcomputer laboratory in the country for teaching writing. She pioneered in computer-assisted composition [CAC], coined the term, and published the first journal in the field (done with desktop publishing). As Vice President of Academic Affairs at Methodist College [now University], she originated the first conference on academic computing in North Carolina. From c. 1983, she consulted and provided keynote addresses, talks, and workshops on academic computing at conferences (e.g., Association for Computers and Humanities, National Educational Computing Conference, National Council of Teachers of English, World Conference on Computers in Education) on campuses across the United States and for organizations (e.g., the AEtna Institute for Corporate Education, the IBM Academic Computing Conference); worked on Bell and Howell's (short-lived) courseware development initiative; and developed (with Drs. Emory Sadler and Wendy Tibbetts Greene) Diagrammatic Writing and Word Processing (software). She later pioneered in the adaptation of Deming and Total Quality to higher education and, with Marshall Thurber et al., held a Deming Workshop on her campus in 1991.
Dr. Sadler has received an Extraordinary Undergraduate Teaching Award (Drake University); a civil rights award from Methodist College's Black Student Movement; the Distinguished Women of North Carolina Award for education (1992); and the Paul Jehu Barringer, Jr. and Sr., Award for Exceptional Service to the History of the State from the North Carolina Society of Historians (2004). She was Visiting Distinguished Scholar in the "Educational Leadership for a Competitive America" seminar of the United States Office of Personnel Management (1992), presented at the First International Milton Symposium in England, and was Director of a National Endowment for the Humanities Summer Seminar for College Teachers on "The Novel of Slave Unrest" held at Bennett College. One of her former Bennett students was responsible for her 2010 selection for the National Women's Hall of Fame.
Lynn's academic publications include five+ books and seventy-two articles, and she has edited twenty-two books/proceedings and three national journals. She edits Footnotes, the journal of the Duplin County Historical Society, and wrote the column "Sadler (But Wiser)" for the on-line newspaper, Lee County Star-Tribune [http://lee.countync.us/columnists], which became state-wide with a change in column title to "North Carolina Notables."
Lynn works full time as a creative writer and an editor. As a poet, she has had nine chapbooks (with a tenth, When A Poet Plays, forthcoming) and four full-length collections published-Snakes in the Sass (humor), Say, Brother, Can You Spare a War? (war; winner, New England Poetry Club 2012 Contest, Shelia Motton Book Award for Book of the Year), To Think of Caves Where Great Whales Breed (animals), and For Shakespeare's Duke Orsino: Music, Food, Love. All, along with Maude Pickett Smith's Hester (historical fiction), which she edited, were nominated for the 2013 Independent Publisher Book Awards. The forthcoming Like a Dragon's Mouth, winner of the RockWay Press Poetry Award, will be a textbook for creative writing, with fiction added. The chapbook Poet Geography won the Lee Witte Poetry Contest and was published in the Mount Olive College Poetry Series (2003). Having to Try won the 2003 Paris Trail Memorial Creative Writing Award of the Albemarle Literary Center. America (chapbook) won Honorable Mention in the 2006 Poets Corner Press Competition and was published in Stockton, CA. To "Talk in That Book" of Nature (principally Native American poems) received the (2005) Charles Dickson Chapbook Prize of the Georgia Poetry Society and was named the 2007 Alabama State Poetry Society Book of the Year. Two collections, Mining and Hearts Divided: Poems of the Civil War, were published (2009) by March Street Press; Winding-Water-Banquets (2011) and Little Rooms (2012; a sonnet collection) by Finishing Line Press. She was invited to be Visiting Scholar/Poet in Israel in December 2001; judged the 2001 Voices Israel International Poetry Competition; was published (2002) in Pudding House's (invitational) National Archiving Project, Poets' Greatest Hits; won The Pittsburgh Quarterly's 2001 Sara Henderson Hay Prize for Poetry; tied for first place in Kalliope's 2002 Sue S. Elkind Contest; was a runner-up for the 2002 Spoon River Poetry Review Editors' Prize Contest; and won the Poetry Society of America's 2003 Hemley Award and Asphodel's 2003 Poetry Contest. Her work appears in the first four anthologies published by California's elizaPress, and she is the featured writer in the second volume, with a separate book of her work [nonfiction] forthcoming. That press named her its "2007 Writer of the Year." She won the 2009 overall award (poetry and fiction) of the San Diego City College National Writer's Contest and City Works Journal. As the Gilbert-Chappell Distinguished Poet 2013-2014 and 2014-2015, she will mentor student poets.
Lynn has had over a hundred short stories published and has won the North Carolina Writers' Network, Talus and Scree, Cream City Review, Rambunctious Review, Cape Fear Crime Festival, and Scratch competitions, with a number of Glimmer Train finalists. One story appeared in Del Sol Press's Best of 2004: The Robert Olen Butler Prize Anthology. Another (on Patrick Swayze) won the Abroad Writers 2006 Competition/Fellowship (France). Her four novels are Tonight I Lie with William Cullen Bryant (Literary Fiction), runner-up for the Dana Award and a finalist in the Florida First Coast Writers' Festival; My Computer Journal of Family Dining [Tragi-comic and Literary Fiction]; Intending to Build a Tower (Mystery); and Long Pig [Science Fiction/Futuristic/Paranormal/Erotic]. The last two received Honorable Mentions in the Florida First Coast Writers' Festival competition. Bards and Sages Press [New Jersey] published the novella, Foot Ways (2007), and the short story collection, Not Dreamt of in Your Philosophy (2008). Lynn was selected for the North Carolina Writers' Network Blumenthal Writers and Readers Series in fiction (1992) and in poetry (2002).
; Carting, in Manhattan (February, 2013).
Locally, in addition to founding the Railroad Festival and writing a newspaper column on Lee County, Lynn was President of the Lee County Council on Women, Arts Council, and The Heart of Carolina Jazz Society; was on the Library Board, Temple Theatre Board; and Board of The Enrichment Center; and is a member of The Sanford Rotary Club. She was named "Rotarian of the Year" in June, 2013. She has edited a book on the Endor Iron Furnace and chaired the 2007 Lee County Centennial, for which she wrote three plays and edited three books: In Celebration of the 2007 Centennial of Lee County: A Collection of Historical Articles and Creative Works, The Lee County 2007 Centennial Calendar of Events, and the Lee County Centennial Historical Calendar (A Calendar in Honor of Lee County's History and People). She was Grand Marshal of the 2007 Jaycees Christmas Parade and loves to cook and, especially, to DANCE.
Dr. Sadler gives readings of her poetry and fiction around the country and likes to write plays (and other works) on commission.
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Missouri lottery winners want to live normally
Mark, left, and Cindy, center, Hill are presented a check by a Missouri Lottery official during the announcement of Powerball winners in Dearborn, Mo., Friday, Nov. 30, 2012. (AP Photo/Orlin Wagner)
DEARBORN, Mo. (AP) — To announce one of the biggest events of their lives together, Cindy and Mark Hill returned to the place where it all began — the high school where they became sweethearts in the 1970s.
Surrounded by family and friends, the two were introduced Friday as winners in this week's huge Powerball lottery — an extraordinary stroke of luck that gives them half of the $588 million jackpot.
The nostalgic high school homecoming seemed to reflect the couple's hopes of staying true to their roots and living simply, at least as simply as possible for winners of one of the biggest lottery prizes in history.
"We will still be going down to the corner cafe for breakfast or fish day. I can guarantee you," Cindy Hill said. "You know it's just us. We're just normal human beings. We're as common as anybody. We just have a little bit more money."
The Hills, who have three grown sons and a 6-year-old daughter, said they don't play the lottery regularly. They spent $10 on five Login to read more
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October 9, 2005
Surviving a killer quake in Pakistan
By Edrees Kakar
Without waiting for instructions from our teachers, we all ran from the building, terrified for our lives.
We had good reason to fear. The massive quake that
registered a 7.6 on the Richter scale killed at least 19,000 people in
I was lucky. My family is safe and my house is intact – so far.
The authorities have warned us that we could experience aftershocks for weeks after the original quake, particularly in the first 48 hours. They can deadly.
By Sunday afternoon, there had been more than 200 aftershocks, some measuring as much as 5.9 on the Richter scale.
Most of the aftershocks were not too strong and people
could not feel them. But we really felt others.
During one of them, I was watching television as my brother slept beside me. When I felt the earth moving again, I woke my brother and got us both out of the house, fast.
But running from the house probably brings more peace of mind than safety.
The houses in my neighborhood – all two-stories high and made of concrete – are close together and small. The streets are narrow, only about five meters wide.
If a building collapsed and we were on the street next to it, it would be dangerous.
It is very difficult to go outside.
The quake, which was centered in the
But families lived there, and reports say 150 people are still underneath it. It was a new building, and residents told television reporters that it collapsed in five seconds.
Rescue teams are now trying to dig through the rubble.
At my school, we students were all inside, just in the second period of the school day, when the quake hit without warning. We all heard it and felt the school shaking. It was a very bad feeling, real dangerous.
We ran outside, and small children were crying. Everyone was scared.
After a short time, school officials told us all to go to our homes.
The news reports are saying it is the largest one in 100 years here.
In my town, only one house collapsed, and it was made of clay. But people are still waiting in fear of the aftershocks.
We cannot sleep. The first night, we got about two hours of rest. No one can sleep calmly because we're all worried about the aftershocks.
My city was spared, with not much damage and nine people dead, but in some towns 90 percent of the houses collapsed, news reports said.
Almost all the cities nearby suffered, with only
On Sunday, a family friend called my house to wake us in the middle of the night to eat before the fast begins. It is Ramadan, and as Muslims, we are fasting. We don't eat between and sundown, which is even more difficult under these circumstances.
The president of
In response, other countries are coming to help.
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The rush to get a Christmas tree is almost underway in St. Lawrence County.
Although most sellers are predicting their biggest sales will be in the next two weekends, some faithful customers wanted to beat the rush and get a tree this weekend.
Scott M. Wallace, Hannawa Falls, picked up a 7-foot tree Sunday at a stand in the Ponderosa Steakhouse parking lot, 185 Market St., Potsdam.
The last few years, Ive waited until two weeks before Christmas and I had to drive all over the county to find one, he said. I dont wait now.
Jeffery W. King and his son Jonathan J. sell Christmas trees from their Balsam Hill Farm in Chateaugay. Every year, they bring truckloads of trees to Ponderosas parking lot, where they sell about 250 trees.
Jeffery King said his father started the trek to Potsdam to sell trees more than 30 years ago and now he took it over, selling trees seven days a week from Black Friday to Dec. 22.
Weve had this relationship with Ponderosa for a long, long time, he said. People buy a tree and go in and eat.
Mr. King said although they only sell trees for a month out of the year, preparing the trees is a yearlong process.
They have to be pruned, you have to mow around them and you have to make sure theres no brush growing through them, he said. Then you have to worry about them getting hit by the frost because it can stunt their growth by two or three years sometimes.
This years weather has been great for tree growers, according to Mr. King.
Mr. King said the next two weekends are going to be very busy for his stand.
We get a lot of the same people back every year, he said. Once you start talking to the people out here, it seems like youve known them for years.
Mr. King said his wife, Glenda, and his mother, Nancy, make Christmas wreaths for him to sell along with the trees.
Ive never come out here before Thanksgiving, but I think my father did because some people like to put a wreath up before Thanksgiving, he said.
John E. Sleeper and Penny R. Summers from Pierrepont got a 7-footer from Mr. King on Sunday. Mr. Sleeper said that although he jokingly threatened his grandchildren to wait until Christmas Eve to buy a tree, he got one early to beat the rush.
There are plenty of last-minute things to do closer to Christmas, he said.
Kingstons Roadside Stand, 2969 County Route 14, Madrid, has featured Christmas trees for the past 10 years. The owner, Don G. Kingston, said he started selling balsam firs the Tuesday before Thanksgiving each year. Next weekend will probably be the peak of our sales, he said.
Mr. Kingston said he buys the fresh-cut trees from a tree grower near Bloomville, and sells them pre-bundled in Madrid. He said he has trees from 5 to 12 feet tall.
Kevin J. Blanchard, Potsdam, and his wife, Jennifer L., have been running Willow Tree Florist and Landscaping on Route 11 in Potsdam for more than 20 years. They said a late Thanksgiving affected their usual Christmas tree sales schedule. It started earlier this year, Mr. Blanchard said. Thanksgiving was late and we sold more trees before Thanksgiving than any previous year.
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