Author: Diana Gitig

Making gene knockouts has long been one of researchers’ favorite ways to determine the function of a gene. If you eliminate a particular gene and it kills the organism, the thinking goes, then that gene must be pretty darn important. Less dramatic ramifications can be equally informative; knockouts have identified genes involved in things like growth, DNA repair, and limb formation.

Knockouts are usually generated in species that are laboratory standbys, like mice and yeast. Creating human knockouts has not really been done for the obvious ethical reasons, not to mention the technical ones (you have to wait 17 years between generations). But ultimately, the whole goal of these studies is to figure out what these genes are doing in humans.

Now a group of geneticists has decided that if you can't make them, you can find them. They've collected and studied human knockouts that have occurred naturally and reported the results in Science.

Randomized, double-blind, placebo-controlled clinical trials are the gold standard for determining if a drug works—or at least if it works better than other drugs that are currently out there. These are the trials in which some people get an intervention for a condition, while similar people get a placebo, and no one (neither the patients nor the doctors) knows who is getting what. The researchers then compare how everyone has fared after a certain amount of time has elapsed.

Patients enroll in these trials to advance medical knowledge and to help future patients by identifying the most effective therapies. But in order to use those therapies, doctors need to be informed of what they are—the results of clinical trials must be disseminated. That, alas, is not really happening so much.

ClinicalTrials.gov is the US government’s repository of clinical trials. It was established in 1997 and made public in 2000. As of September 2007, the FDA stipulated that all clinical trials of drugs, biologics, and devices had to be registered on the database within three weeks of enrolling their last participants. The results of the trial had to be registered within a year after the trial’s completion.

The immune system of an adult is shaped by both genetic factors and every microbe we've ever been in contact with. The result is a unique set of things we can recognize, called an immunorepertoire. Environmental influences—things like infections and age—are thought to account for at least half of the differences in our individual immunorepertoires.

Since these nongenetic factors can, in theory, be manipulated more readily than genetic ones, it might be nice to know what they are and how precisely they impact our immune systems. A study published this week in Nature aims to look into just that.

Researchers looked at the different compositions of immune cell types in 638 healthy Caucasian Belgians ranging in age from two to 86. They found that different healthy people have a different complement of immune cells. Immature precursor cells are the most variable between individuals; while activated, mature cell types are more similar.

Agriculture is not responsible for the bulk of worldwide greenhouse gas emissions; that honor goes to more fossil-fuel intensive activities like transportation and generating electricity. Even still, greenhouse gas emissions from global agriculture are climbing by 1 percent a year.

Humans did once upon a time live without HDTVs and Hummers—we could do so again, at least in theory—but people will always have to eat. This makes reducing agricultural emissions particularly difficult. Researchers in the UK have reported that an approach called "land sparing" farming could offset the emissions coming from agriculture by sequestering carbon.

Land sparing increases the efficiency of existing farming practices, allowing more food to be produced on less land. The surplus farmland is then allowed to revert to a “natural” habitat. It all sounds sensible, and the paper led to a number of news articles earlier this month.

One of the more exciting developments in cancer research involves tweaking the immune system to attack cancer. It's possible to engineer the immune system's T cells to attack and kill tumor cells based on the specific proteins those tumors produce. It's a relatively new anti-cancer therapy, but initial tests have shown it to be clinically effective, especially against leukemias (wherein B cells become cancerous).

But as with chemotherapy, the side effects are severe—when immune cells run amok, bad things can happen. The T cells raised to fight the tumor can elicit what's called a "cytokine storm," setting off an intense immune reaction. They can also overstep their bounds to kill all of a patient's B cells rather than just the cancerous ones.

One of the most promising strategies employed to alleviate these side effects is to make the anti-tumor T cells dependent upon a ”switch.” Rather than using one of the T cell's normal receptors to latch on to cancer cells, it's possible to engineer one that only sticks in the presence of an exogenous small molecule—drug-dependent killing, in effect. This way, the T cell is only activated in the presence of the switch molecule, which can be administered or removed at will or dosed as desired.

Functional magnetic resonance imaging (fMRI) is used to record activity in different brain regions. When different regions exhibit simultaneous activity, we generally conclude that they are functionally connected in a network. Functional connectivity maps derived this way have revealed networks that control things like sensory processing and others that control cognition.

But this approach has a significant limitation: it's unable to reveal which brain region within the network is influencing which. Things happen so fast relative to the time resolution of the imaging that it's impossible to tell which part of the brain was active first.

Information about the direction of signaling—effective connectivity, rather than just functional connectivity—has been difficult to obtain. But now researchers in Germany have developed a method that combines the undirected functional-connectivity information from fMRI scans with energy metabolism data from PET scans, which measure glucose use, to begin to identify this effective connectivity.

Let's get something straight from the start: vaccines are good. Let's be completely clear about that. But sometimes some people have adverse reactions to them—no, not autism, but things like diarrhea, nausea, fatigue, maybe a sore arm. And when the vaccinated (or their parents) complain to their friends about it, their friends might be tempted to skip their own vaccinations.

It would be nice to know in advance who might respond negatively to a vaccine so they could be warned and treated. A recent paper out of London harnesses advances in high-throughput analytical technologies, informatics, and biostatistics to begin to do just that.

Researchers treated 178 healthy adult volunteers with a vaccine against the H1N1 "swine flu" that circulated in 2009. They took blood and urine from the volunteers one week before their shots, the day of their shots, and then one day, one week, two weeks, and again 63 days afterward.

Over the past couple of years, American labs have been caught mishandling biological samples that require extreme care: things like smallpox, anthrax, and avian flu. Largely in response to this, the White House issued a memo this past October 29 that outlined its vision of our future biosecurity and safety.

But in last week's Science, a trio of academics from Stanford lamented that the memo's approach was insufficient. Their exact criticism: “It grafts recommendations onto inadequate institutional structures and fails to address underlying systemic needs.”

When those assorted labs screwed up in their own distinctive ways, each was shut down and reviewed on a narrow, individualized basis. It is definitely great that the White House recognized that a more systematic, centralized approach is necessary but, according to this critique, they have not provided it.

Porcine reproductive and respiratory syndrome (PRRS) gives pigs a fever and cough, but it costs American swine farmers over $600 million a year. Vaccines have been ineffective at fighting it, as has breeding pigs to be resistant. Last year, researchers in the Midwest used CRISPR-Cas9-based gene engineering to generate pigs that lack CD163, the protein that PRRS uses to infect its target cells in pigs. Now, the same team just demonstrated that the pigs lacking the receptor don't get sick when exposed to PRRS.

The three resistant pigs had deletions in both copies of their CD163 genes and thus made no CD163 protein. This lack did not seem to affect them in any adverse way. After weaning, these three and eight wild-type piglets were exposed to the strain of PRRS virus usually used in experimental infections, which happens to be a pretty virulent one.

The pigs were generated at the University of Missouri but infected at Kansas State University—the Kansans who did the infecting didn't know which pigs were which, making this what's called a blinded experiment. All of the pigs were kept in the same pens, so even if the initial infection didn't take, the pigs had plenty of opportunities to get sick from each other.

Thirteen percent of newborns with congenital heart disease (CHD) also have congenital abnormalities that don't affect the heart. This is twice the rate at which they appear in newborns without heart problems. Infants with CHD are also at an increased risk of neurodevelopmental disorders later in life, like motor, social, language, and cognitive impairments.

These elevated risks were thought to be caused by poor circulation during gestation or the stresses imposed by postnatal therapies. But a new study suggests that both types of abnormality are actually due to mutations in genes highly expressed in the developing heart and brain. Results are published in Science.

Researchers looked at the protein-coding DNA (called the exome) of 1,213 babies with CHD and their unaffected parents. The results were compared to 900 control babies and parents. They looked for new mutations that appeared only in babies with CHD, babies with CHD accompanied by extracardiac congenital abnormalities, babies with CHD and neurodevelopmental disabilities, or both.