Inicio Blog Página 19

Scientist ‘reprograms’ roving immune cells in Alzheimer’s research

0

Because it would be damaging to extract microglia directly from the skulls of Alzheimer’s patients, USC Stem Cell scientist Justin Ichida’s group is taking a far less invasive approach. Using small samples of patients’ blood or skin, the team is applying a technique called “reprogramming” to transform these cells into microglia.

“We’ve used this approach to produce functional nerve cells and other cell types, but not microglia, so this will be a first,” said Ichida, who also uses reprogramming to study ALS and frontotemporal dementia.

Ichida’s team will then use a gene-editing tool called CRISPR to introduce two genes associated with Alzheimer’s disease into the patient-derived microglia.

The researchers will observe how these two genes alter the function of the microglia. These genetic changes could cause a variety of problems, such as triggering inflammation or preventing microglia from cleaning up defective proteins known as amyloid plaques, which are implicated in Alzheimer’s disease.

In addition to revealing how the two Alzheimer’s-related genes affect the function of microglia, the project will pave the way for other researchers to study microglia on a patient-specific basis.

A positive partnership

Ichida’s team is taking a look at the role of microglia in the onset of Alzheimer’s with support from a $100,000 gift from the John Douglas French Foundation.

A longtime champion of such innovative approaches to Alzheimer’s research, the John Douglas French Foundation has given more than $2.5 million to USC. The gift to the Ichida Lab honors Michael Minchin Jr., who retired from his role as the foundation’s president and CEO in 2016.

The work of Ichida’s lab is supported by the John Douglas French Foundation. “Their partnership enables us to make new strides toward helping the 5.5 million Americans living with this debilitating and often fatal disease,” said Ichida, assistant professor of stem cell biology and regenerative medicine.

Source: Science Blog

Listado de emisiones anteriores

No se encontraron entradas.

Phosphorus-containing lipid molecule self-assembles into a cuboid structure

0
Artist's impression of the observed phospholipid cubes. The molecules are so closely packed that the membrane can scarcely be bent, resulting in the cuboid shape. Credit: Moser Graphic Design moser.ch

Phospholipids play an important role in living organisms, forming membranes, among other things. The new findings enhance the understanding of the forces acting within biological membranes and could open up new pathways in medicine. The researchers headed by Andreas Zumbühl from the University of Fribourg in Switzerland present their results in the journal Angewandte Chemie.

Their special chemical structure allows phospholipids to self-assemble to form membranes consisting of two connected layers of molecules. These are a key component of the biological membranes that separate the various parts of a living cell. Membranes made of phospholipids can also automatically form three-dimensional, enclosed structures, for example in water where they produce so-called vesicles.

Normally, such vesicles are spherical in shape, to minimise the surface tension. However, the 1,2-diamidophospholipid now analysed by the scientists produces cuboid vesicles at room temperature. This is because this phospholipid forms very close-packed and therefore very stiff layers, which are very difficult to bend, thanks to special bonds, known as hydrogen bonds, which minimise the distance between the molecules. When it assembles as a three-dimensional structure, the membrane continues to favour flat surfaces and structures having as few edges as possible, conditions that are satisfied by a cube.

Its unusual structure could make this phospholipid interesting for medical applications, for example to deliver drugs to specific parts of the body. “The edges of the cube are formed by the outer molecular layer, whereas the inner layer has a discontinuity here. This membrane defect means that the structure may break there if the cube is shaken,” explains Zumbühl. A drug that has been encapsulated in the cube can therefore be released in a controlled fashion. “One might for example encase a drug that dissolves blood clots and use this in an emergency after a heart attack. High shear stresses would be exerted on the cube in a blocked artery, releasing the drug at precisely the location where it can do the most good,” says Zumbühl. The cube currently being studied is not itself suitable for such applications, however, since it is as yet too fragile.

Phospholipid cubes like these could one day be used for targeted drug delivery. The edges of the cube are its weakest point, so that it can be opened by shaking or applying larger forces, releasing the enclosed substance when and where it is needed. Credit: Moser Graphic Design moser.ch

For the team of research scientists, the phospholipid examined is most of all an important step on the way to a greater objective: “We would like to understand what forces are acting in the membrane, so that we can later deliberately influence these. This would allow us to use phospholipids as a kind of building material, so as to construct specific structures on a cellular level,” says Zumbühl. To understand the precise details of the phospholipids, the scientists synthesise certain molecules, modifying their structure and properties slightly each time, in order to see what effect this has. Because a small change in the structure of a phospholipid can have a large effect.

The beamline P08 at DESY’s X-ray source PETRA III had to be specially equipped for these kind of structural investigations at the boundary between air and water. “Thanks to the optimisation of our set-up and the exact control of the temperatures and pressures acting on the membranes, even the surface pressure in an individual layer of the 1,2-diamidophospholipid could be determined,” explains beamline scientist Olof Gutowski from DESY, who made these measurements possible. The result surprised the scientists: “For 30 years, it has generally been assumed that the pressure in a biological membrane must be relatively high, around 30 Millinewton per metre,” says Zumbühl. “In the membrane we studied, however, the pressure must be considerably lower, around 5 to 10 Millinewton per metre. This calls into question the long-standing rule of thumb.”

Source: Phys.org

Zika virus successfully diagnosed from semen

0

“This assay can help reduce Zika infection rates and allow couples who are identified at risk due to travel or geographic location plan their pregnancy,” said lead author Hisham Greiss M.D., Ph.D., HCLD at the Fertility and Cryogenics Lab.

A total of 100 semen samples were spiked with a recombinant Accuplex ZIKV (SeraCare Life Sciences) at 5 viral copies per ml and processed in Aptima Urine Transport medium (Hologic Inc.) and tested using Aptima® ZIKV assay released under the FDA’s emergency use authorization on the fully automated Panther system from Hologic, Inc. The samples were also tested for West Nile Virus, Chagas and Dengue, recombinant Dengue Virus, recombinant Chikungunya Virus, Human Papilloma Virus, Herpes Simplex Virus 1, Herpes Simplex Virus 2, Chlamydia, and Gonorrhea. The experiment was repeated three times and in triplicates each time.

The assay was found to be 100% sensitive and 100% specific to ZIKV RNA from semen samples with a limit of detection of 5 viral copies per mL of semen.

Zika fever symptoms are often misdiagnosed due to its nonspecific clinical symptoms, so an accurate diagnosis is of paramount importance for management of the disease and to prevent neonatal infections. Zika infection during pregnancy can also cause serious birth defects and is associated with other pregnancy problems.

There was no external funding received for this work.

Source: ASM

Lactobacillus from yogurt inhibits multidrug-resistant bacterial pathogens

0

The inhibitory substance is a unique, bacteriocin-like peptide that is heat stable up to 121°C. Bacteriocins are antimicrobial peptides produced by bacteria and released to kill other related bacteria that are not immune to their action.

“Considering the current upsurge of antibiotic resistance in hospitals, especially among the gram-negative bacteria, and the exigent need to find viable alternatives, findings from the study may hold promise for possible therapeutic application,” said Rachelle Allen-McFarlane, doctoral candidate in the Biology Department at Howard University, Washington, D.C.

Lactobacillus parafarraginis KU495926, identified by 16S rRNA, was isolated from a sample of commercial yogurt on de Man-Rogosa-Sharpe agar by standard plate count technique under anaerobic conditions. The isolate exhibited the typical lactic acid bacterial characteristics: gram positive, catalase, oxidase, and motility negative. Screening of the antimicrobial activity by spot and well-diffusion assays showed that the isolate inhibited the growth of several multidrug-resistant/extended-spectrum β-lactamase gram-negative bacterial pathogens from a local hospital.

Analyses of the extract by fast-perfusion liquid chromatography (FPLC), SDS-PAGE, and PCR (polymerase chain reaction) suggested that the inhibitory agent is a bacteriocin.

The research was conducted in the laboratory of Dr. Broderick Eribo, in the Biology Department at Howard University, Washington, DC. Drs. Winston Anderson, Adrian Douglas Allen, Ayele Gugssa, Ms. Garima Bansal and June Prout, all affiliates of Howard University, also contributed to this work.

Source: ASM

Clostridium difficile: To Test or Not to Test (and How?)

0

Viewpoint. These findings emphasize the importance of appropriately selecting patients for C difficile testing, including clinical evaluation for signs and symptoms consistent with CDI, as well as alternative causes of diarrhea. A major strength of this study was that the assignment of pretest probability was based on prospective evaluation by a study physician (with interviews and physical examinations), rather than on retrospective medical record review. Given the implications for hospital surveillance, as well as potential inappropriate treatment in asymptomatically colonized patients, consideration of the pretest probability of CDI for patients in the decision to perform C difficile testing is critical.

Testing Asymptomatically Colonized Patients

Terveer and colleagues evaluated the performance characteristics of C difficile tests in asymptomatically colonized patients. The investigators compared the performance of a commercially available polymerase chain reaction (PCR) directed to toxin A and B, a commercially available enzyme-linked fluorescent assay (ELFA) to glutamate dehydrogenase (GDH), and an in-house developed PCR vs a gold standard of toxigenic culture. Testing was performed using 765 stool samples obtained from asymptomatic patients admitted to three hospitals.

Overall, 5.1% of samples were positive for C difficile, and 3.1% contained toxigenic C difficile. The GDH ELFA and both PCR tests demonstrated high negative predictive values (>99%). However, the positive predictive values were low (34.7% for the GDH ELFA and 31.9% for the commercially available PCR test).

The investigators commented that these performance characteristics suggest that these assays would be useful as a first screening test but that the low positive predictive values would preclude their use as stand-alone tests.

Viewpoint. This study contributes to the literature on performance characteristics of C difficile tests in asymptomatically colonized patients, although it should be noted that the prevalence of C difficile colonization in this cohort was somewhat lower than that reported in other studies.

Source: MedScape

CRISPR Eliminates HIV in Live Animals

0
Methodology used by the investigators in the current study. [Yin et al., Molecular Therapy, 2017]

Yet now, new data released from a research team led by investigators at the Lewis Katz School of Medicine at Temple University (LKSOM) and the University of Pittsburgh shows that HIV DNA can be excised from the genomes of living animals to eliminate further infection. Additionally, the researchers are the first to perform this feat in three different animal models, including a “humanized” model in which mice were transplanted with human immune cells and infected with the virus. Findings from the new study were published recently in Molecular Therapy in an article entitled “In Vivo Excision of HIV-1 Provirus by saCas9 and Multiplex Single-Guide RNAs in Animal Models.”

This is the first study to demonstrate that HIV-1 replication can be completely shut down and the virus eliminated from infected cells in animals with a powerful gene-editing technology known as CRISPR/Cas9. The new work builds on a previous proof-of-concept study that the team published in 2016, in which they used transgenic rat and mouse models with HIV-1 DNA incorporated into the genome of every tissue of the animals’ bodies. They demonstrated that their strategy could delete the targeted fragments of HIV-1 from the genome in most tissues in the experimental animals.

“Our new study is more comprehensive,” noted co-senior study author Wenhui Hu, M.D., Ph.D., associate professor in the Center for Metabolic Disease Research and the department of pathology at LKSOM. “We confirmed the data from our previous work and improved the efficiency of our gene-editing strategy. We also show that the strategy is effective in two additional mouse models, one representing acute infection in mouse cells and the other representing chronic, or latent, infection in human cells.”

In this new study, the LKSOM team genetically inactivated HIV-1 in transgenic mice, reducing the RNA expression of viral genes by roughly 60% to 95%—confirming their earlier findings. They then tested their system in mice acutely infected with EcoHIV, the mouse equivalent of human HIV-1.

“During acute infection, HIV actively replicates,” explained co-senior study investigator Kamel Khalili, Ph.D., professor and chair of the department of neuroscience at LKSOM. “With EcoHIV mice, we were able to investigate the ability of the CRISPR/Cas9 strategy to block viral replication and potentially prevent systemic infection.” The excision efficiency of their strategy reached 96% in EcoHIV mice, providing the first evidence for HIV-1 eradication by prophylactic treatment with a CRISPR/Cas9 system.

In the third animal model, a latent HIV-1 infection was recapitulated in humanized mice engrafted with human immune cells, including T cells, followed by HIV-1 infection. “These animals carry latent HIV in the genomes of human T cells, where the virus can escape detection, Dr. Hu explained. Amazingly, after a single treatment with CRISPR/Cas9, viral fragments were successfully excised from latently infected human cells embedded in mouse tissues and organs.

In all three animal models, the researchers employed a recombinant adeno-associated viral (rAAV) vector delivery system based on a subtype known as AAV-DJ/8. “The AAV-DJ/8 subtype combines multiple serotypes, giving us a broader range of cell targets for the delivery of our CRISPR/Cas9 system,” remarked Dr. Hu. Additionally, the researchers re-engineered their previous gene-editing apparatus to now carry a set of four guide RNAs, all designed to efficiently excise integrated HIV-1 DNA from the host cell genome and avoid potential HIV-1 mutational escape.

To determine the success of the strategy, the team measured levels of HIV-1 RNA and used a novel and cleverly designed live bioluminescence imaging system. “The imaging system, developed by Dr. Won-Bin Young while at the University of Pittsburgh, pinpoints the spatial and temporal location of HIV-1-infected cells in the body, allowing us to observe HIV-1 replication in real time and to essentially see HIV-1 reservoirs in latently infected cells and tissues,” stated Dr. Khalili.

The researchers were excited by their findings and are optimistic about their next steps. “The next stage would be to repeat the study in primates, a more suitable animal model where HIV infection induces disease, in order to further demonstrate the elimination of HIV-1 DNA in latently infected T cells and other sanctuary sites for HIV-1, including brain cells,” Dr. Khalili concluded. “Our eventual goal is a clinical trial in human patients.”

Source: GEN

Antibody Makes Alzheimer’s Protein Detectable in Blood

0
Caption: The protein tau (green) aggregates abnormally in a brain cell (blue). Tau spills out of the cell and enters the bloodstream (red). Research shows that antibodies (blue) can capture tau in the blood that reflect its levels in the brain. Credit: Sara Moser

Brain imaging and spinal taps can also help to look for signs of the disease. But an absolutely definitive diagnosis of Alzheimer’s disease is only possible today by examining a person’s brain postmortem. A need exists for a simple, less-invasive test to diagnose Alzheimer’s disease and similar neurodegenerative conditions in living people, perhaps even before memory loss becomes obvious.

One answer may lie in a protein called tau, which accumulates in abnormal tangles in the brains of people with Alzheimer’s disease and other “tauopathy” disorders. In recent years, researchers have been busy designing an antibody to target tau in hopes that this immunotherapy approach might slow or even reverse Alzheimer’s devastating symptoms, with promising early results in mice [1, 2]. Now, an NIH-funded research team that developed one such antibody have found it might also open the door to a simple blood test [3].

Scientists know that tau loosened from abnormal tangles exits the brain and enters the bloodstream. Testing for the protein in blood has been extremely difficult because it disappears almost immediately. But the team has discovered that tau proteins bound to antibodies remain in the bloodstream much longer, allowing them to reach easily detectable levels. Importantly, they show that those blood levels of tau provide a good indication of abnormal tau levels in the brain. The discovery suggests a simple blood test for tau could one day be used to screen patients for early signs of tau-associated conditions, including Alzheimer’s disease and a brain injury known as chronic traumatic encephalopathy (CTE) that can affect football players and boxers who have suffered repeated concussions.

In a study published in Science Translational Medicine, the team led by David Holtzman at Washington University, St. Louis, showed that an infusion of its anti-tau antibody into people and mice causes blood levels of tau to rise within a day or two. In fact, during studies of three people with a rare neurodegenerative disease called progressive supranuclear palsy, they found that a single dose of antibody caused tau levels to remain high for up to 2 weeks.

Further study showed that the antibody increases blood levels of tau by stabilizing the protein and not allowing it to disappear so quickly. When tau alone was injected into the bloodstream, half of it vanished in less than 10 minutes. But when tau was injected along with the antibody, the protein remained in the blood for more than 3 hours. In other words, the antibody acts like a caretaker, making tau easier to measure by amplifying the time it stays in the bloodstream.

Of course, tau levels in the blood would only be useful if they provide an accurate indication of what’s going on in the brain. To find out, the researchers tested tau levels in mice with brain injuries. The injuries caused an increase in tau in the brain fluid that also appeared in their blood. Similarly, in mice genetically modified to develop less tau in brain fluid with age, the researchers found that blood levels of the protein indeed declined as the animals got older.

While lots of work remains to be done, Holtzman notes that the next logical step is to pair this promising new blood test with clinical trials to prevent or slow Alzheimer’s disease. One promising partner would be the Accelerating Medicines Partnership-Alzheimer’s Disease (AMP-AD) Biomarkers Project, which has brought together four pharmaceutical companies and NIH’s National Institute on Aging. AMP-AD is already incorporating tau imaging into trials of several promising therapies, and adding the blood test could be a powerful way to assess its clinical utility.

References:

  1. Anti-tau antibodies that block tau aggregate seeding in vitro markedly decrease pathology and improve cognition in vivo. Yanamandra K, Kfoury N, Jiang H, Mahan TE, Ma S, Maloney SE, Wozniak DF, Diamond MI, Holtzman DM. Neuron. 2013 Oct 16;80(2):402-14.
  2. Anti-tau antibody reduces insoluble tau and decreases brain atrophy.Yanamandra K, Jiang H, Mahan TE, Maloney SE, Wozniak DF, Diamond MI, Holtzman DM. Ann Clin Transl Neurol. 2015 Mar;2(3):278-88.
  3. Anti-tau antibody administration increases plasma tau in transgenic mice and patients with tauopathy. Yanamandra K, Patel TK, Jiang H, Schindler S, Ulrich JD, Boxer AL, Miller BL, Kerwin DR, Gallardo G, Stewart F, Finn MB, Cairns NJ, Verghese PB, Fogelman I, West T, Braunstein J, Robinson G, Keyser J, Roh J, Knapik SS, Hu Y, Holtzman DM. Sci Transl Med. 2017 Apr 19;9(386)

Links:

Source: NIH

IFCC’s Forthcoming Congresses – April Issue

0

Calendar of IFCC Congresses/Conferences and Regional Federation’s Congresses

10 – 11, 2017 Satellite Meeting “Management of Inborn Errors of Metabolism: from Diagnosis to Treatment” – EuroMedLab Athens 2017   Athens, GR
 Jun 10, 2017 Satellite Meeting “Metabolic Bone Disease: The Role of the Clinical Laboratory” – EuroMedLab Athens 2017   Athens, GR
Jun 11 – 15, 2017 XXII IFCC-EFLM EUROMEDLAB – ATHENS 2017 Athens, GR
 Jun 15 – 16, 2017 IFCC Satellite Meeting “Biomarkers for Diabetes” – WorldLab Durban 2017 Athens, GR
Sep 17 – 22, 2017 XXIII COLABLIOCLI Congress 2017 and XI Uruguayan Congress of Clinical Biochemistry Punta del Este, UY
 

Oct 20 – 22, 2017

 

XIV International Congress of Pediatric Laboratory Medicine

 Durban, ZA
Oct 21, 2017 IFCC-POCT Satellite Meeting – WorldLab Durban 2017  Durban, ZA
Oct 22 – 25, 2017 XXIII IFCC WORLDLAB – DURBAN 2017 Durban, ZA
 Oct 26-27, 2017 IFCC Satellite Meeting “Biomarkers for Diabetes” – WorldLab Durban 2017  Durban, ZA
May 19 – 23, 2019 XXIII IFCC-EFLM EUROMEDLAB – BARCELONA 2019 Barcelona, ES
May 24 – 28, 2020 XXIV IFCC WORLDLAB – SEOUL 2020 Seoul, KR

Calendar of events with IFCC auspices

May 02 – 06, 2017

Workshop and Course in clinical microbiology update.2017

Quito, EC

May 04 – 05, 2017 22nd Annual Conference and Continuing Professional Development (ACCPD)   Jimma, ET

May 10 – 13, 2017

2nd Conference of Romanian Association of Laboratory Medicine

Timisoara, RO

May 10 – 12, 2017

II.Turkish In Vitro Diagnostic (IVD) Symposium, BIOMARKERS

Izmir, TR

May 11 – 13, 2017

The VIII Baltic Transfusion Medicine Congress and the I Latvian Congress in Laboratory Medicine

Riga, LV

May 17 – 18, 2017

9th European Symposium on Clinical Laboratory and In Vitro Diagnostic Industry “Stat Tests in Clinical Laboratory”

Barcelona, ES

May 30 – 31, 2017

VI International Symposium Clinical Laboratory and Quality

Barcelona, ES

Jun 11 – 14, 2017

44°Congresso Brasileiro de Analises Clinicas

Joao Pessoa, Paraiba, BR

Aug 22 – 25, 2017

72°Congreso de Bioquimica 2017

Buenos Aires, AR

Sep 19 – 21, 2017

18th International Metrologie Congress

Paris, FR

Sep 21 – 22, 2017

13th EFLM Symposium for Balkan Region

Belgrade, SRB

Oct 04 – 07, 2017

3rd International Symposium on Advances in Circulating Tumor Cells (ACTC)

Rhodes, GR

Oct 05 – 06, 2017

CELME 2017

Prague, CZ

Oct 11 – 13, 2017

III Russian Congress of Laboratory Medicine

Moscow, RU

Oct 18 – 20, 2017

LMCE 2017 & KSLM 58th Annual Meeting

Seoul, KR

Nov 30, 2017

11th International Scientific Meeting of the Centree of Metrological Traceability in Laboratory Medicine (CIRME) “Measurement Uncertainty in Medical Laboratories: Friend or Foe?”

Milan, IT

Jun 12 – 15, 2018

XXXVI Nordic Congress of Clinical Chemistry

Helsinki, FI

ISLH 2017 Workshop: Platelets Revisited

0

Attending the XXXth International Symposium on Technical Innovations in Laboratory Hematology? Take part in Siemens Healthineers luncheon workshop, Platelets Revisited.

Date: May 4, 2017

Time: 12:00–1:30 p.m.

Location: Room 319 AB. Hawaii Convention Center. Honolulu, Hawaii

Learning objectives:

  • Identify inherited versus acquired thrombocytopenia
  • Distinguish among the different causes of inherited thrombocytopenia
  • Explore a new method of counting reticulated platelets

Lunch boxes will be provided.

Agenda:

Contribution of Automated Parameters in the Diagnosis of Platelet Disorders. Speaker: Prof. Marie-Christine Alessi—Biological Hematology Service, CHU Timone, Marseille, France

Learn how laboratory investigations can help resolve practical challenges presented when identifying inherited versus acquired (immune) thrombocytopenia and distinguishing among the different causes of inherited thrombocytopenia.

Reticulated Platelets (RPs) for Differential Diagnosis of Thrombocytopenia and Beyond. Speaker: Doctor Florian Prüller—Medical University of Graz, Austria

Explore the derivation, function, and clinical significance of reticulated platelets and a new method of counting them and other byproducts.

Information: healthcare.siemens.com.ar

 

Agenda

       

Radio El Microscopio

Ze Xiong

Últimas notas publicadas