Nikmat Perasaan

Jika kita terasa gembira kita harus bersyukur,

Jika Kita terasa sedih kita harus bersyukur,

Jika kita terasa marah kita harus bersyukur,

Jika Kita terasa cinta kita harus bersyukur,

Kerana Allah memberikan satu nikmat yang besar, iaitu mempuanyai perasaan

Second week - Histopathology and Cytology Lab

6 June- 10 June 2011 : The second week of industrial training. During this period, I have learned something new.     I learn what exactly histopathology and cytology is? Histopathology is the microscopic examination of tissue in order to study manifestation of disease. Cytology or more correct terminology using for this lab is cytopathology which is the study of cellular disease and use of the cellular change for diagnosis of diseases. Before I explain more about my experiences, I would to divide this article to several part which; general steps of histopatholgy and cytopatholgy, Histopatholgy( H and E staining), Cytopatholgy (Papanicalou staining and Wright staining), How to distinguish benign, and metastic tumour in breast cancer (histopatholgy).

General steps of Histopatholgy and Cytopatholgy

The figure below shows the general steps of histopathology and cytopathology. First step is the sample fixation. This step is crucial to get good microscopic slides. Second steps, is only for histopathology which is sample processing. The next step is sample staining. This steps basically to distinguish which part of cell are nucleus or cytoplasm. Last but not least is microscopic examination.

Histopathology

The histology samples from patients have several steps in order to diagnose their cells. It is involved several steps which; 1- sample fixation with formalin, 2- sample processing, 3- sample staining. and 4- Microscopic examination.

1: Sample Fixation

Sample fixation is a crucial step in histology studies. Fixation is a chemical process by which biological tissues are preserved from decay, either through autolysis or putrefaction. Fixation terminates any ongoing biochemical reactions, and may also increase the mechanical strength or stability of the treated tissues. Fixation of tissue is done for several reasons. One reason is to kill the tissue so that postmortem decay (autolysis and putrefaction) is prevented. Fixation preserves a sample of biological material (tissue or cells) as close to its natural state as possible in the process of preparing tissue for examination. To achieve this, several conditions usually must be met:

First, a fixative usually acts to disable intrinsic biomolecules – particularly proteolytic enzymes—which otherwise digests or damages the sample.Second, a fixative typically protects a sample from extrinsic damage. Fixatives are toxic to most common microorganisms (bacteria in particular) that might exist in a tissue sample or which might otherwise colonise the fixed tissue. In addition, many fixatives chemically alter the fixed material to make it less palatable (either indigestible or toxic) to opportunistic microorganisms.

Finally, fixatives often alter the cells or tissues on a molecular level to increase their mechanical strength or stability. This increased strength and rigidity can help preserve the morphology (shape and structure) of the sample as it is processed for further analysis. In this cases, the sample from patient is immersed in 10% formalin.

2: Sample processing

To provide slides for microscopic examination, the sample must be process first. This step involved another several steps. First is sample grossing- Is the process referred to as grossing a specimen, where tissue specimens taken from routine surgical cases, autopsies, or other scientific investigations are examined, described and trimmed to proper size. The grossing method is vary from hospital to hospital. From this lab, the sample that fixed by 10% formalin is cut. The part of sample that being cut is depend on pathologist. Pathologist may choose the tumour part or healthy part as control.

Next step is sample dehydration by tissue processor which is automated or can be done manually.  The aim of Tissue Processing is to remove water from tissues and replace with a medium that solidifies to allow thin sections to be cut. Biological tissue must be supported in a hard matrix to allow sufficiently thin sections to be cut. For light microscopy, paraffin wax is most frequently used. Since it is immiscible with water, the main constituent of biological tissue, water must first be removed in the process of dehydration. Samples are transferred through baths of progressively more concentrated ethanol to remove the water. This is followed by a hydrophobic clearing agent (such as xylene) to remove the alcohol, and finally molten paraffin wax, the infiltration agent, which replaces the xylene.The sample processing firstly immersed in formalin for 30 minutes twice, after that in Alcohol solution for 1 hour six times, next in xylene for 1 hour 3 times and in wax also 1hour  3 times.

Next is the embedding step. After the tissues have been dehydrated, cleared, and infiltrated with the embedding material, they are ready for external embedding. During this process the tissue samples are placed into molds along with liquid embedding material (such as agar, gelatine, or wax) which is then hardened. This is achieved by cooling in the case of paraffin wax and heating (curing) in the case of the epoxy resins. The acrylic resins are polymerised by heat, ultraviolet light, or chemical catalysts. The hardened blocks containing the tissue samples are then ready to be sectioned.

Because Formalin-fixed, paraffin-embedded (FFPE) tissues may be stored indefinitely at room temperature, and nucleic acids (both DNA and RNA) may be recovered from them decades after fixation, FFPE tissues are an important resource for historical studies in medicine. The last step for sample processing is the sample sectioning by microtome. This step can be divide by 2 which are trimming and sectioning. This step provide thin slide for microscopic examination.

3: Sample staining

Before we observed the morphology of cell/sample under microscope, first we must stained the sample. In histopathology studies, the routine stain is Haematoxylin and Eosin stain (H &E). The purpose of H & E staining is to distinguish the nucleus and cytoplasm. Haematoxylin which stains blue or purple on nuclei. Haematoxylin is oxidative agent that positively charged and bind to negatively charged phosphate on nuclear-DNA. Eosin which stains pink to red blood cell or connective tissue in cytoplasm. Eosin is acidic colourant that mainly bind to protein.Besides routine H & E staining, it is also has another type of staining which histochemistry staining and Immunohistochemistry staining. The need to do the staining is depend on the patient cases and diseases.

4: Microscopic examination

Under the light microscopes, the pathologist can observed the morphology of the cell to determine the type of tumour whether benign or malignant, the level of certain cancer and whether the tumour are metastatic or not.

Cytopathology

Cytology laboratory test can be divide by two which “Gynecological  Cytology” and “non-gynecological cytology”. This is the test that everyone known by as “Pap Smear”. It name comes from the Papanicolau test for cancer cells, developed in the 1940’s. Smears are made from cells collected from the cervix of the uterus, stained, and then examined microscopically for evidence of any abnormal cells. Non-gynecological cytology can be body fluid such as sputum,urine and spinal fluid and also fine needle aspiration.

Cytology samples are fixed in 95% alcohol at least for 30 minutes. After that, the samples are stained by Papanicalou stain. After staining, observed the morphology under  light microscope.

Principle of Papanicolou staining

       It is involves five dyes in three solutions, A nuclear stain, haematoxylin, is used to stain cell nuclei. The unmordanted haematein may be responsible for the yellow color imparted to glycogen.First OG-6 counterstain (-6 denotes the used concentration of phosphotungstic acid; other variants are OG-5 and OG-8). Orange G is used. It stains keratin. Its original role was to stain the small cells of keratinizing squamous cell carcinoma present in sputum.

Second EA (Eosin Azure) counterstain, comprising three dyes; the number denotes the proportion of the dyes, eg. EA-36, EA-50, EA-65. Eosin Y stains the superficial epithelial squamous cells, nucleoli, cilia, and red blood cells. Light Green SF yellowish stains the cytoplasm of all other cells. This dye is now quite expensive and difficult to obtain, therefore some manufacturers are switching to Fast Green FCF, and however it produces visually different results and is not considered satisfactory by some. Bismarck brown Y stains nothing and in contemporary formulations it is often omitted.

How to distinguish the benign tumour and malignant tumour in the cases of breast cancer

From this lab, what interesting that I can learn is how to distinguish benign tumour and malignant tumour specific to breast cancer. During practical here, I try to compare between various slides of breast cancer patients and observed the doctor comment on the patients. By H & E staining, we know that Haematoxyline stain purple on nuclei, so that under microscopic observation I try to observed nuclei morphology on benign tumour and malignant tumour.

From microscopic observation, the nuclei in benign tumour cell are big, and clump together in one place but in malignant tumour, nuclei very small and disperse in all cytoplasm or tissues. The presence of nuclei in all tissues indicates that the tumour is invasive (malignant tumour).

Benign Breast Tumour

Malignant Breast Tumour

Diagnostic Microbiology Lab

30 May - 3 June 2011-  First week of industrial training!! My first rotation at diagnostic microbiology lab. Here the very interesting things that learned from here was how to translate the knowledge of microbiology for diagnostic purposes. In order to explain what exactly I learned from this lab, I divide to 2 part which ; The principle of Gram staining and Identification hierarchy.

Principle of Gram staining

Gram staining was introduced by Danish scientist called Hans Christian Gram (1853-1938) in 1884 to distinguish between Pneumococci and Klebsella pneumonia bacteria. Until now, no others staining can replaced the Gram staining as major tools to detection of bacteria. The purposes of gram staining is to distinguish between Gram positive and Gram negative bacteria. 

Gram staining has 4 basic steps; First the application of primary stain (crystal violet) to a heat-fixed smear of bacterial culture, followed by the addition of a mordant (iodine), after that rapid decolourisation of alcohol or acetone and lastly counterstain with safranin or basic fuchsin.

How gram staining can distinguish between gram positive and gram negative bacteria. Gram positive bacteria have a thick mesh cell wall made of peptidoglican and gram negative bacteria have thin layer of peptidoglican with additional outer membrane layer made of lipid. Crystal violet (CV) dissociate in aqueous solution to form CV+ ion and Cl- ion. These ion penetrate through the peptidoglican cell wall and cell membrane of both gram positive and gram negative bacteria. The CV+ ion interact with negatively charged components of bacterial cells and stain cells purple.

Iodine (I- or I3-) interact with CV+ and form large complex of crystal violet and iodine ( CV-I). When decolourization with alcohol  is added, it interact with the lipids of cell membrane. A gram negative bacteria will lose its outer membrane and the peptidoglican layer is left exposed. The CV-I complexes are washed from the membrane. In contrast, a Gram-positive cell becomes dehydrated from ethanol treatment. The large CV-I complexes become trapped within Gram-positive cell due to the multilayer nature its peptidoglican. After the decolourisation step, the Gram-positive bacteria remains purple and the Gram-negatives loss its purple colour. Counterstain, which is usually postively charged safranin is applied last to give decolorised Gram-negative bacteria a pink or red colour.

In clinical diagnostic purpose, it  is important to distinguish between Gram-positive and Gram negative bacteria is to screen the pathogen. Most Gram-negative bacteria are pathogenic but not in Gram-positive bacteria. Gram-positive bacteria depend on species of bacteria, type of samples, and also how they colonized  part of the body. If certain bacteria colonized to much in one area of the body, it may due to immunodeficiency that cause recurrent bacteria infection. After we identify whether it Gram-positive or Gram negative bacteria, to identify the specific species of bacteria we followed the identification hierarchy.

Bacteria Identification Hierarchy


After we stain bacteria via Gram staining and observe under the microscope, we can distinguish whether this is Gram positive bacteria or Gram negative bacteria. After that we followed the bacteria identification hierarchy to screen which specific bacteria species whether its pathogenic or not? Bacteria identification hierarchy can be divided by two which Gram positive  bacteria identification and gram negatives identification  hierarchy:

The figure above shows the identification hierarchy for gram-positive bacteria. By observing the gram-staining of bacteria culture under microscope, if the bacteria cultured stained purple, we observed its morphologwhether it shape cocci or bacilli, if cocci we can further down the hierarchy whether its Staphylococcus or Streptrococcus. So Catalase test must be done to both of them. The principle of  catalase test is all the Staphylococcus bacteria have catalase enzyme with act on hydrogen peroxide to release oxygen.  In this test, we can observed the immediate bubbles.

After we know the bacteria is Staphylococcus, we further down the hierarchy, at this point this is very important. Because we must do Coagulase test to distinguish whether the bacteria culture is the Staphylococcus aureus or not. S.aureus is well known dangerous pathogenic bacteria. Because the bacteria culture from patient sample, this is important to know whether the patient have S.aureus or not. The principle of coagulase tests is to know whether the bacteria have coagulase enzyme or not? S.aureus contain coagulase enzyme which catalyze the formation of fibrin clot in plasma. In this test we can observed the clotting/ clumping formation

The figure below is the gram negative bacteria identification hierarchy. As mentioned above, most of gram negatives bacteria are pathogenic. To identify the specific gram neagtive bacteria, just follow the identification hierarchy.

Both Gram-staining and Identification Hierarchy is the basic knowledge of diagnostic microbiology. Actually that has more diagnosis. For example, biochemical test and also sensitivity test. Right now, the more fast and accurate in bacteria identification that available in kit such as API test kit. As conclusion, what I learned from the industrial training in diagnostic microbiology laboratory is how I see the very simple Gram staining principle  is very useful in diagnosis of diseases. Furthermore, in analysis what exactly bacteria infect the patient, besides we analyse what the type of bacteria  in patient's samples, we must know the medical history of patient and also we must observed whether the bacteria is colonized enough in patient body to be considered its pathogenic.

Clinical Diagnostic

It time for Industrial training !! One of elective course in Genetic and Molecular Biology Bsc. program of  University of Malaya. I choose this course for  completing my degree because perhaps I learn something that can increase my knowledge and experience.

Its true!! This industrial training like an oasis of knowledge.From 30 May 2011- 22 July 2011, my industrial training begin at Advanced Medical And Dental Institutes (AMDI)  . Generally my industrial training all about clinical diagnostic. Within 8 weeks, my task is to do lab rotation per week which diagnostic microbiology lab, histopathology and cytology lab, haematology lab, chemical pathology lab and lastly at genetic lab. from 6-8 weeks, this duration for mini-project.

The exposure to the clinical diagnostic give me an excitement. From the beginning, my education style always about theory. In University of Malaya, it has different approach, they related knowledge with research. But the exposure to clinical diagnostic makes me see the science world bigger. It make me feel every second in my routine life is about science.Besides that clinical diagnostic makes me more appreciate about how important to keep our body in good health!!!

Education and correlation with cancer survival.

An interesting data that I get from American Cancer Society , which is the risk factor of prostate cancer can be divide by 3  categories; ages, ethnicity and socioeconomic among the American. In summary, the men with ages 50 years and above and African American are more likely to get prostate cancer.


In the socioeconomic, the study of death rates vary among the years of education especially, African American men. In the range of 25- 64 years of education, American Cancer Society found that  the death rate of African American men with 12 or fewer years of education was twice from the men more that 12 years education. In the white men, the rates with 12 years and fewer with more than 12 years is 1.5 times. 


By the data, its look like longer a person have education, more change to survive for prostate cancer. What exactly its means. In my opinion, longer they have education, they have increase their awareness in preventing cancer such as their food, lifestyle with smoking and alcohol free, early cancer diagnosed  with frequently medical check up and also have more understanding how the cancer cause, and the best treatment.

" AKU YANG SENTIASA MENYESAL"

Tersebut al-kisah. Iskandar Zulkarnain dan tenteranya terpaksa mengharungi terowong yg panjang dan gelap. Tiada api dan cahaya.Di tengah perjalanan, mereka terpijak batu2 yg begitu banyak bertaburan. Ada org berkata, terowong ini kaya dgn emas dan berlian.Apa lagi. Ada org yg mula mengutip batu2 tersebut hingga penuh tangan. Ada yg guna kan baju utk dijadikan pemegang batu2. Ada juga yg tidak percaya dan tidak mengutip apa.

 Setelah sekian lama berjalan dlm gelap, ada di antara mereka merasa letih lalu melepaskan batu2 yg mereka bawa.Akhirnya mereka mula nampak di hujung terowong. Dlm samar2 mereka telah lihat, batu2 yg mereka bawa adalah betul2 emas dan berlian.Ada yg minta kebenaran dari Iskandar utk berpatah balik ke tengah terowong. Tapi tak dibenarkan. 

Bila mereka keluar dari terowong, maka penyesalan yg amat hebat terasa oleh tentera2 Iskandar

Semua menyesal. Tiada yg tak menyesal. 

1. Paling menyesal ialah yg tidak percaya langsung. Tiada langsung emas berlian yg dibawa walaupun mempunyai peluang. 

2. Yg bawa sikit pun menyesal. "Kenapa lah aku bawa penuh tangan saja. Aku patut gunakan baju, kain dsb utk angkut emas dan berlian"

‎3. Yg bawa penuh baju pun menyesal. Aku patut pinjam kain2 dari org lain. Aku patut gunakan mulut utk angkut emas berlian dsb dsb. 

4. Yg paling menyesal juga yg mula2nya percaya. Tapi half way lepaskan batu2 kerana tidak yakin dan kerana letih dan malas

Begitu lah gambaran penyesalan kita bila sampai ke alam AKHIRAT. Semua menyesal. Tiada yg terkecuali.. Ketika sakaratul maut, kita akan dinampakkan gambaran di mana nasib kita di akhirat. Ketika tu roh kita meronta2 tidak mahu meninggalkan dunia jikalau gambaran yg tidak baik ditunjukkan. Spt mereka yg meronta2 utk balik ke tengah terowong dan minta kebenaran utk balik semula. Tapi bila roh di halqom sudah terlambat.

Bila sampai di akhirat, semua org akan menyesal. Yg soleh dan solehah menyesal kerana masa yg berlalu tanpa dimanafaatkan untuk meningkatkan amal ibadat supaya dapat darjat yang lebih tinggi. Yang kadang2 soleh, kadang2 perangai mcm KAFFIR Laknatullah  lagi lah menyesal. Ada amalan. Tapi sikit. Dosa menimbun.

Org2 kafir lah yg paling menyesal. Terutama mereka yg dah sampai seru, faham pasal Islam, tapi pilih utk tidak beriman kerana ego, pangkat dan harta dsb. Orang yg asal nya Islam tapi meninggalkan agama lagi lah menyesal. Spt mereka yg mula2 kutip batu, tapi lepaskan. Di akhirat nanti mereka lah yg paling menyesal.

Itu lah gambaran penyesalan di Akhirat. Diceritakan penyesalan mereka dlm Surah Sajadah. 

Ahli Neraka merayu pada Allah. 'Wahai Tuhanku, sesungguhnya kami telah lihat dan dengar kedahsyatan akhirat, kembali lah kami ke dunia utk beramal soleh, sesungguhnya kami telah benar2 yakin.

Ditulis oleh pak cik saya Azhan Ali melalui status facebooknya : sebagai seorang mahasiswa juga menyesal selepas exam:

1- budak rajin dan genius merasa menyesal kerana masa yang dibuang untuk perkara-perkara lagha tidak digunakan untuk memahami ilmu dengan lebih supaya dapat first class degree atau 4.00 cgpa dan boleh dapat scholar penuh tuk sambung Phd

2- yang kadang-kadang belajar, kadang-kadang fly class pun menyesal gak pasal pointer cukup-cukup makan

3- yang asyik nk pi clubbing, terlalu sibuk dengan aktiviti-aktiviti bukan akademik,meniaga MLM selagi x cukup orang bwhn x nmpk btng hidung kt lecture,  terlalu extreme bab politik kampus pun menyesal gak pasal member-member dah pesan.. enjoy enjoy jugak, belajar kena la jugak. memang politik tue penting tapi jangan sampai hilang tujuan masuk U... akhir sekali dapat la G.K (gagal keluar)

Demi Masa sesunguhnya manusia dalam kerugian kecuali mereka yang beriman dan beramal soleh, -pesan dengberpesan pesan dengan kebenaran berpesan kesabaran.

SEBAGAI PERINGATAN BUAT DIRI YANG SENTIASA LALAI DAN SENTIASA DALAM PENYELESALAN

Darah Rakyat

Darah rakyat masih berjalan
Menderita sakit dan miskin
Bila datangnya pembalasan
Rakyat menjadilah hakim


Ayuh! Ayuh!
Berjuang sekarang
Kemerdekaan sudah datang
Merah panji-panji kita
Merah warna darah rakyat
Merah warna darah rakyat


Mereka bersumpah pada rakyat
Kemiskinan pasti hilang
Kaum kerja akan membina
Dunia baru pasti datang
Dunia baru pasti datang

Ayuh! Ayuh!
Berjuang sekarang
Kemerdekaan sudah datang
Merah panji-panji kita
Merah warna darah rakyat
Merah warna darah rakyat

Biofuel still have hopes.... But a lot thing we must do

Biofuel is renewable, clean and enviroment friendly. However the cost to extract it from biomass are very high and economically inefficient compare to fossil fuel. Energy company did not have any choice to choose fossil fuels eventhough fossil fuels are major culprit of global warming and increasing global greenhouse gases. But is not the omega of biofuels research.

By indentify additional enzyme that can  digest cellulose efficiently can help to develop biofuels in industrial scale.Living in cow rumen, the uncultured microorganisms is highly effective at degrading plant cell wall. Hess et al. (p. 463) used metagenomics and single-genome sequencing to assemble draft genomes from microbes adhering to rumen-incubated switchgrass to identify nearly 28,000 genes related to known biomass-degrading families. Ninety candidate carbohydrate-degrading enzymes were synthesized and their activity analyzed against 10 different substrates, including the biofuel crops miscanthus and switchgrass. The data set greatly expands the repertoire of full-length genes available for use in industrial biotechnology.

Within 28000 genes we must narrow-down to more specific group in order to find what the exactly the important addtional enzymes. In order to translate those genes, must involved a lot of molecular technique and of course involves many parties. Molecular Biology knowlegde can't stand alone without intergrated with other field such as biochemistery and microbiology.

With knowledge of genetic integrated with biochemistry in determining biological or enzyme pathway to degrade the cellulose plus microbiologist to understanding the behaviour of microbes, we can find alternatives way to produced biofuel that are very effective and econimically effective. Come on Bioligist, Lets work together for bettter future.

What we can observe via Pseudogenes?

Pseudogenes are dysfunctional relatives of known genes that have lost their protein-coding ability or are otherwise no longer expressed in the cell(Pseudogenes). In other word, pseudogenes is the genes contains same/similar exons but lack of introns of functional genes. A genes become pseudogenes once the enough mutation accumulated. 


What the importances of pseudogenes? After I read article from scientific american ( sci-am), in summary this articles explain about on the human evolution. Human accumulates pseudogenes so that reducing the ability of smell and grew more for vision. Different people has different pseudogenes, That why is explain the different perception of odour for different people like "You smell flower, I smell stale urine". Each of us live on our olfactory world. “Everybody’s olfactory world is a unique, private world,” says Andreas Keller, a geneticist at the Rockefeller University.


Genetic variability contribute to different behavioral variability.   When  Keller and his colleagues asked 500 people to rate a panel of 66 odors for intensity and pleasantness, they gave the full range of responses—from weak to intense and from pleasant to unpleasant. In an ongoing study at the University of Dresden, Thomas Hummel and his associates have tested 1,500 young adults on a panel of 20 odors and found specific insensitivities to all but one—citralva, which has a citrus smell. Based on these findings, Keller suspects that each person has an olfactory blind spot.


These studies have wider implications than smell, said geneticist Doron Lancet of Israel’s Weizmann Institute of Science. Because several genes contribute to the detection of most odors, understanding the genetics of olfaction and the way mutations spread in a population is yielding insights into the mechanisms of poly­genic diseases such as coronary heart disease and diabetes.

Besides that, is that Pseudogenes also contribute in development of one species? Compare the tiger and the house cat. The house cat like the miniature sizes of tiger. On the evolution pathways, may be pseudogenes can explain the how the tiger evolved to cat in term of developmental genetic.


Just take a look the Purring mechanism. ( Purr).  The cat from Felis genus is the only cat can purr. On other big cat species, felids of the Panthera genus (Tiger, Lion, Jaguar and Leopard) also can purr. The subdivision of the Felidae also can "purr" or can more suitable word is roaring. The roaring cat differ with the purr cat based on hyoid anatomy. The ‘roaring cats’ (lion, Panthera leo; tiger, P. tigris; jaguar, P. onca; leopard, P. pardus) have an incompletely ossified hyoid, which according to this theory, enables them to roar but not to purr. 

However  the snow leopard (Uncia uncia, or P. uncia), as the fifth felid species with an incompletely ossified hyoid, purrs (Hemmer, 1972). All remaining species of the family Felidae (‘purring cats’) have a completely ossified hyoid which enables them to purr but not to roar. However, Weissengruber et al. (2002) argued that the ability of a cat species to purr is not affected by the anatomy of its hyoid, i.e. whether it is fully ossified or has a ligamentous epihyoid, and that, based on a technical acoustic definition of roaring, the presence of this vocalization type depends on specific characteristics of the vocal folds and an elongated vocal tract, the latter rendered possible by an incompletely ossified hyoid.


If we observe the pseudogenes in cat and related with tiger we can understand more about the evolution of cat in purring mechanism, on the other hand better understanding of developmental genetic.

mitochondria- a new tools to observe diseases

Mitochondria, the cell energy powerhouse. The energy in the form of ATP produced many metabolism in the body's system and help in control the signal transduction process. Mitochondria also play role in proper cell death called   apoptosis- Intrinsic pathway of initiation, cytochrome C from mitochondria associated with APAF activate the ProCaspase 9 to Caspase 9 to activate the caspase cascade.



Mitochondria also can fuel the development of many chronic and poorly understood conditions, including cancer, heart disease, and neuro degenerative disorders such as Parkinson’s and Alzheimer’s. The disease process begins  when environmental factors such as polluted drinking water or cigarette smoke perturb mitochondria, causing cellular levels of high-energy molecules called reactive oxygen species to spike.


Scientists have long assumed that wounded mitochondria release reactive oxygen molecules, which then damage DNA and proteins, increasing disease risk. But some of the environmental chemicals that harm mitochondria produce these dangerous molecules themselves, prompting a “cause-and-effect question,” explains James M. Samet, a toxicologist at the National Health and Environmental Effects Research Laboratory in Chapel Hill, N.C., who has co-authored a study on the new technique in the journal Environmental Health Perspectives.


Until now  how this destructive cascade unfolds still unclear. But researchers have developed an imaging technique that shows, in real time, what happens when things start going awry—a tool that could help doctors diagnose mitochondrial injuries before they have the chance to do serious cellular
damage.


To do this, the researchers coaxed three fluorescent molecules into the mitochondria of living human skin cells. One lit up in the presence of hydrogen peroxide, a prominent reactive oxygen species, whereas the other two acted as mitochondrial injury sensors. Next they exposed the cells to a mitochondrial toxicant. The damage sensors lit up first, with the hydrogen peroxide marker following moments later, suggesting that the reactive oxygen.

Eventhough the more validation is necessary but this diagnosis will help them to understand the genesis of chronic diseases.

Ikhlas itu misteri

Kebelakangan ini saya banyak membaca tentang cerita-cerita tentang keajaiban ikhlas. Antaranya dart nota-nota rakan-rakan di facebook serta cerita-cerita dari mulut-mulut orang.

Yang terbaru, baru pagi tadi ketika sedang mengulangkaji human genetik, terbaca satu nota dari facebook dari kenalan agak mengharukan hati saya apabila nota itu menceritakan keikhlasan seorang budak berumur 11 tahun dalam mengedarkan risalah jalan ke syurga hingga dapat menyelamatkan seorang wanita dari membunuh diri dan memeluk agama Islam ( http://www.facebook.com/note.php?note_id=437569086946&id=1343475216&ref=mf)

Selain itu ada cerita tentang keikhlasan seorang  dalam menyampaikan dakwah dimana dia sentiasa membawa fikir bagaimana untuk mengislamkan salah satu kawasan yang penduduknya yang tidak ada langsung pendedahan tentang Islam. Sampainya dia di kawasan itu untuk menjalankan dakwah, tiba-tiba dia dipeluk oleh ang wanita. Apabila di tanya mengapa, wanita itu bermimpi bahawa jika datang lelaki ini kahwinilah dia dan ikutilah agamanya. Akhirnya lelaki itu mengislamkan wanita itu, keluaganya, mengahwiniya serta lama-kelamaan satu kawasan itu masyarakatnya memeluk Islam.

Sesunguhnya hak Allah untuk memberi hidayah. Bagaimana caranya terserah pada Allah. Fikir tentang dakwah, ikhlas semata-mata kerana Allah adalah maksud dan tujuan hidup seorang muslim.

Ikhlas juga kadangkala menukar persepsi seseorang. Ini adalah pengalaman sendiri. Ketika darah muda bergelora, pemahaman dan pemikiran diracuni oleh kem-kem motivasi yang mencucuh api perkauman menyebabkan bencinya terhadap kaum lain-lain meluap-luap. Terus-terang kem rhetorik orang tua yang berfikiran sempit yang mengatakan kaum itu memang kaum pengkhianat dan macam-macam lagi dan menyebabkan menghukum secara total kaum itu. Mungkin segelintir ada.

Ketika itu sedang habis membeli belah di pasaraya di ibu negara, berjalan ke stesen LRT, dalam hati apabila terpandang kaum itu, menyumpah dan memandangnya dengan pandangan benci. Tidak tahu macam mana, mungkin Allah nak beri petunjuk tentang keburukan sikap assabiyah ini, terjatuh dan menyebabkan barang-barang belian berterabur. Bergegas 1 pasangan kekasih kaum yang dibenci itu membantu saya.

Mungkin sedikit ikhlas dari mereka menyebabkan apabila saya pulang, saya berfikir sejenak tentang semangat perkauman yang melampau dalam diri adalah sia-sia. Saya mula berfikir, rasis adalah racun, Kita apabila hidup bersama dalam sebuah negara haruslah berdamai dan berkongsi. Bukan saling mencurigai yang membawa kepada kemusnahan pada negara disatu masa kelak.

Ketika itu saya mengubah persepsi saya bahawa prejudis terhadap bangsa lain melampau akan membawa padah. Sedikit nukilan dari hamba yang lemah.

3 Simple Tips to boost our brain

Our brain the  precious organ in our life. So sometimes we need do some routines to boost our brain. This is important especially to prevent diseases such as Alzheimer.

First step, learn a or some music instrument. Learning how to play an instrument brings about a dramatic brain changes that not only improve music skills but also other cognitive ability such as language,speech, memory, IQ and even empathy.  No wonder  during I was practice my guitar lesson, I feel my brain so heavy, ( not heavy like I do some mathematic homework), this is the process how the brain to develop. So for me, I need to start back my guitar lesson in order to boost my brain.

Second step, eat healthy food. Brains need some chemical to boost up the brain development. Brain's booster food such as raisins and vegetables help in increase our cognitive ability. Practice without support by food or chemical slower the brain development.

Third step, a little exercise. Exercises makes blood can flow enough to brain. The blood brings oxygen that important in cell respiration. Have a light exercise such as jogging or walking or plays some sports is good for our brain and also for our healthy. Just make yourself sweat.

Gorilla, the possible of the origin of human Malaria parasite P. falciparum

 

When the emergence of disease outbreak, first thing that in scientists or epidemiologists mind are the resources or disease reservoirs are from our phylogenetic closely related species, chimpanzees. But recently the scientists found the different story on the origin of human Malaria P.falciparum, which is from gorilla.

A research team led by virologist Beatrice Hahn of the University of Alabama, Birmingham, used the polymerase chain reaction to amplify Plasmodium DNA from a whopping 2739 fecal samples from chimpanzees,gorillas, and bonobos.

Using single-template amplification strategies and a much larger collection of ape specimens than previously analysed, the scientists show here that wild-living chimpanzees and western gorillas are naturally infected with at least nine plasmodium species. Among more than 1,100 SGA derived mitochondrial, apicoplast and nuclear gene sequences from 80 chimpanzee and 55 gorilla samples, they found a total of nine sequences that were related to P. malariae, P. ovale or P. vivax. All others grouped within one of six chimpanzee or gorilla-specific lineages representing distinct Plasmodium species,three of which had not previously been described. Significantly, all currently available human P. falciparum sequences constitute a single lineage nested within the G1 clade of gorilla parasites. This indicates that human P. falciparum is of gorilla origin, and not of chimpanzee , bonobo or ancient human origin, and that all known human strainsmay have resulted froma single cross-species transmission event.

From the finding, what is still unclear is when gorilla P. falciparum entered the human population and whether present-day ape populations represent a source for recurring human infection.(when date of the jump from gorillas to humans). Plasmodium does not mutate much, she explained, making it difficult to calibrate a so-called molecular clock that enables evolutionary biologists to back-calculate the timing of a pathogen moving from one species to another.

According to Ajit Varki, an evolutionary biologist at UC San Diego,  he believes a human gene mutation, CMAH, which arose about 2 million years ago, may provide a clue to how and when the jump occurred. The mutation changes sialic acid receptors on red blood cells, rendering them much less susceptible to P. reichenowi, and Varki suspects that the gorilla P. falciparum similarly would have great difficulty infecting human cells.

This is also support by Michael Worobey, an evolutionary biologist who has also focused on the origin of the AIDS epidemic, is similarly intrigued that gorilla P. falciparum has not repeatedly infected humans. The finding can help clarify the evolutionary history of P. falciparum.

(for more information please read the article on Natures magazines 23rd september 2010, "Origin of the human malaria parasite Plasmodium falciparum in gorillas")

Almost Indistinguishable, different in function.

If you see 2 amino acid sequence that just a 1-2% slightly different on the sequence, can we just ignore their differences and simply said the protein will be same with the same 3-D confirmation. Don’t simply make the easy conclusion like that because the slightly different can describes a lot.

One such of puzzle is related to the mammalian cytoskeletal protein β- and γ-actin, whose amino acid sequences are 98% identical.  The slightly difference of both protein make they differ in protein modification which β-actin is modified by addition of arginine (arginylation) and γ-actin is not modified, resulting the distinct role for each in the cell.

Scientists try to understand this phenomenon. This is unexpected example of the protein whose the properties are determined at the nucleotide rather than amino acid level, forcing a reassessment of what defines a synonymous change in the gene sequence.

Arginylation of certain protein occur after translation of their termini. Although discover in 40 year ago, the effect of the argynilation is fully understood than other posttranslational modifications. Proteins are arginylated during normal cell growth and in response to stress, and arginylation has been associated with protein degradation in the proteasome. One prominent group of substrates is actin group but not all actin groups are argynilated in posttranslation modification.

Selective modification of the actins is important for normal cell morphology and migration because the absence of arginylation  substantially decrease intracellular actin cellular level and changes its partial segregration.

In this case, the arginylation of β-actin on the posttranslation makes β-actin preferentially localizes at the protruding leading edge of a migrating cell, where rapid actin polymerization pushes the cell’s front forward. There, β-actin is present as a loose and branched arrangement of relatively short actin filaments. By contrast, γ-actin is found in the cell body in dense nonbranched networks and long contractile stress fibers that impart morphological stability and support cell adhesion.

Because of their slightly different of amino acid sequence they affect the rate of translation, and affect their polypeptide modification and also their stability.

What exactly the differences of their amino acid sequences that affect the translation rates.  As mentioned above to explain this is not in amino acids level but in nucleotide levels. The γ-actin contain high frequency of codon that slower the translation but the same region of codon, the alternate codon that coding same amino acid in β-actin is make the translation faster.

Fast translation allows only arginyation, thereby stabilizing the protein. In contrast slow translation allows both arginylation and ubiquitination occur that leading to fast degradation. In conclusions, the synonymous  mutation that encode same amino acid is again not exactly same in the protein comfirmation and modification.

Ada hikmah disebalik teguran PERKASA pasal isu masuk masjid Teo Nie

Politik Malaysia, isu-isu yang akan menjadi tumpuan adalah isu-isu agama dan isu perkauman. Kebelakangan ini Pribumi Perkasa Negara (PERKASA) ada menimbulkan isu tentang kebiadaban ahli parlimen Serdang, Teo Nie yang memasuki masjid tanpa menutup aurat dan ini seakan menghina Islam walaupun niat Teo Nie baik, untuk menyampaikan sumbangan kepada masjid.

Apabila isu ini dihebah-hebahkan. Jentera politik pembangkang membalasnya dengan mempersoalkan tentang kebiadaban beberapa wanita pemimpin negara yang tidak menutup aurat didalam masjid. Dengan pendedahan itu, pembangkang menggunakan modal agar pihak kerajaan tidak menggunakan isu ini untuk membedil pembangkang. Lihat photo dibawah:

Kalau dibandingkan dengan Teo Nie, ini lebih teruk. Kerana mereka dalam photo ini merupakan orang Islam, tahu buka aurat haram. Saya tak tahu la orang didalam photo ini pakai tudung ikut mazhab apa, tapi yang jelasnya sebagai penduduk di alam Melayu Nusantara, kita pengikut Mazhab Syafie, aurat perempuan harus ditutup seluruh badan kecuali muka dan tapak tangan.

Kita pergi kepada tajuk tentang hikmah disebalik teguran PERKASA. Saya ada terbaca artikel dalam selangor kini tentang cadangan Hasan Ali untuk membuat peraturan yang lebih terperinci tentang masuk masjid.http://www.selangorkini.com.my/my/berita/16660

Kita lihat dari sudut positif, teguran PERKASA membuat semua pihak membuka mata tentang peraturan dan adab untuk masuk masjid yang selama ini tidak diendahkan. Dengan adanya teguran, barulah pemimpin-pemimpin politik yang selama ini asyik bertekak dengan isu-isu politik remeh mengambil inisiatif untuk meningkatkan pengurusan sistem masjid khususnya negeri Selangor.

Akan tetapi, teguran PERKASA bagi saya agak kasar dan terburu-buru sehinggakan boleh menimbulkan salah faham tentang Islam. Orang yang bukan Islam akan melihat Islam ini tidak terbuka kerana tidak membenarkan orang bukan Islam masuk masjid jika dibandingkan dengan gereja.

Saya ingin menegaskan disini, tidak salah orang bukan Islam masuk masjid asalkan mengikut peraturan yang digaris pandu oleh Islam. Isu Teo Nie saya rasa bukan salah dia, ini disebabkan sistem pengurusan  institusi masjid. Sepatutnya mereka lebih peka tentang ini contohnya memberikan Teo Nie jubah untuk menutup aurat seperti di masjid Putrajaya.

Saya harapkan kerajaan Negeri Selangor dan negeri-negeri lain dapat menaik taraf sistem pengurusan masjid agar orang bukan Islam boleh menyertai aktiviti-aktiviti masjid agar pemahaman mereka pada Islam lebih mendalam.

"ISLAM ITU SEJAHTERA"

The power of Mother’s Love

Love is something abstract.  We can’t measure love. Love is something did not have any unit. Some people relate love with Einstein’s relativity theory. But first what are relativity theory is? According to the theory, energy and matter are relative and light is constant.

Giving an example, the 2 cars, Car A moving in 60 km/h and Car B moving 80 km/h. Doesn’t care about the direction of the both cars, 2 of them are relatively moving in 20 km/h difference.  One spotlight from a building is focusing to both cars. The light moving to both cars is constant. Thus, same with love, love is constant. We love every one that we love constantly. No more or no less. That is how they relate the love with the physics.

It’s enough to elaborate love in scientific way.  Let’s discuss about the topic, the power of mother’s love. Some people believe, when some teenager’s suicide cases because of stress, failure, and many more reasons because of they did not have enough love from parent or the parental ignorance. But how this believe support by scientific evidence. I would like to say in the genetics’ point of view.

In 2004, Szyf and Meaney published a paper in Nature Neuroscience that helped launch the behavioral epigenetics revolution. It remains one of the most cited papers that journal has ever published. The paper built on more than a decade of research in Meaney’s  lab on rodent mothering styles.

Meaney had found that the type of mothering a rat receives as a pup calibrates how its brain responds to stress throughout its life. Rats raised by less-nurturing mothers are more sensitive to stress when they grow up. When confined to a Plexiglas tube that restricts their movement, for example, they exhibit a greater surge in corticosterone, a hormone pumped out by the adrenal glands in times of stress. The likely cause is reduced numbers of a receptor for steroid hormones in the brain. This so- called glucocorticoid receptor is part of a negative feedback loop that dials down the volume on communication between the brain and adrenal glands, thereby reducing reactivity to stress.

The Nature Neuroscience paper linked this reduction in glucocorticoid receptors to DNA methylation. Rats raised by less nurturing moms tended to have more methyl groups attached to the promoter region, the “on” switch, of the glucocorticoid receptor gene. These methyl groups block access by the transcription factors that turn the gene on. As a result, fewer receptors are produced. Subsequent experiments showed that enzymes that reverse DNA methylation of the glucocorticoid receptor gene also reverse the effects of unenthusiastic mothering on the offspring’s hormonal and behavioral responses to stress.

Several of Meaney’s students have carried on with this work and extended it in new directions. Frances Champagne, a co-author of the 2004 paper, went on to show that female rats raised by nurturing mothers are more nurturing mothers themselves. She also found that pups raised by less-nurturing moms exhibit greater methylation—and reduced expression—of the gene for a particular estrogen receptor in the hypothalamus, a brain region involved with reproductive behavior. This receptor amplifies signaling by oxytocin, a hormone that promotes mother-infant bonding.

Summarize from their finding, rat raised by less nurturing mother (not enough love) likely to sensitive to stress because of reduction the glucocorticoid gene activity that reducing reactivity of stress— more DNA methylation that repress the transcription of the gene.

The scientific evidence support that the important of mother’s love. But don’t blame to their mother if have suicide cases. A lot of factors that causing stress. The important point is the finding gives us a guidance to care more about our children and never ignore them. Happy families can build a happy society that lead to the peace.

The renaissance of DNA Drugs

“Rise and rise again, until lambs become lions”. The meaning of this phrase is never give up until we achieve our goals.

Why I write this post because I would like to show my appreciation to the scientists who are optimist in developing DNA drugs after the false start. DNA Drugs is the vaccine contains plasmid that carried DNA sequence of the pathogen, so that the immune system can produce antibody as preparation to fight the infection of the disease.

Why I mean the “false start” is because the DNA Drugs has the head-to-head  competition with another potential vaccine that using adenovirus as carrier of DNA of pathogen seems not very effective with the latter vaccine. The competition is their compare the immune response of two vaccines. The DNA Drugs contains plasmids, each carrying a gene for one of five HIV proteins. Its goal was to get the recipient’s own cells to make the viral proteins in the hope they would provoke protective reactions by immune cells. The second vaccine used another virus called an adenovirus as a carrier for a single HIV gene encoding a viral protein.

The DNA recipients displayed only weak immune responses to the five HIV proteins or no response at all, whereas recipients of the adenovirus-based vaccine had robust reactions. To academic and pharmaceutical company researchers, adenoviruses clearly looked like the stronger candidates to take forward in developing HIV vaccines.

What I say they are optimistic, after the disappointing result of DNA drugs they did not just give up, they find what are the mistakes. The main reasons for those failures seemed to be that vaccine plasmids were not getting into enough cells and, where they did penetrate, the cells were not producing enough of the encoded proteins. As a result, the immune system was not being sufficiently stimulated.

The vaccines using adenovirus seems have a bigger problem. In 2007 pharmaceutical company Merck initiated a large trial of an HIV vaccine that used an adenovirus called AdHu5 to deliver HIV viral genes. In light of the potent immune responses seen in previous experiments with adenoviruses, great hope and excitement surrounded the beginning of this test, known as the STEP trial. In all, about 3,000 HIV-negative individuals received the vaccine or a placebo shot.

As the trial progressed, though, a disturbing difference between the two groups began to emerge: people who got the vaccine were no better protected than those who received the placebo, and eventually they appeared to be more vulnerable to being infected by HIV. As a result they found that 49 out of 914 men in the vaccine group became HIV-positive, whereas 33 out of 922 men in the placebo group did. With this realization, in the summer of 2009 the STEP trial was halted.

The STEP trial gives the scientists to look back on the DNA Drugs. To optimize the DNA Drugs effect, the scientist suggest the several steps as visualized on the figured below:

As conclusions, if we fail now is doesn’t means we fails forever. Keep trying and never give up.