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•The insulin growth factor 2 (IGF2) is abundantly expressed in the brain.•Inappropriate IGF2 expression is implicated in a growing number of diseases.•There is a correlation between ...IGF2 and memory performance in humans and animals.•IGF2 is proposed as a new target to treat cognitive disabilities.•We highlight the potential of external IGF2 administration as a pro-cognitive agent.
Insulin-like growth factor 2 (IGF2) is abundantly expressed in the central nervous system (CNS). Recent evidence highlights the role of IGF2 in the brain, sustained by data showing its alterations as a common feature across a variety of psychiatric and neurological disorders. Previous studies emphasize the potential role of IGF2 in psychiatric and neurological conditions as well as in memory impairments, targeting IGF2 as a pro-cognitive agent. New research on animal models supports that upcoming investigations should explore IGF2′s strong promising role as a memory enhancer. The lack of effective treatments for cognitive disturbances as a result of psychiatric diseases lead to further explore IGF2 as a promising target for the development of new pharmacology for the treatment of memory dysfunctions. In this review, we aim at gathering all recent relevant studies and findings on the role of IGF2 in the development of psychiatric diseases that occur with cognitive problems.
Complex human traits are influenced by variation in regulatory DNA through mechanisms that are not fully understood. Because regulatory elements are conserved between humans and mice, a thorough ...annotation of cis regulatory variants in mice could aid in further characterizing these mechanisms. Here we provide a detailed portrait of mouse gene expression across multiple tissues in a three-way diallel. Greater than 80% of mouse genes have cis regulatory variation. Effects from these variants influence complex traits and usually extend to the human ortholog. Further, we estimate that at least one in every thousand SNPs creates a cis regulatory effect. We also observe two types of parent-of-origin effects, including classical imprinting and a new global allelic imbalance in expression favoring the paternal allele. We conclude that, as with humans, pervasive regulatory variation influences complex genetic traits in mice and provide a new resource toward understanding the genetic control of transcription in mammals.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SBMB, UILJ, UKNU, UL, UM, UPUK
Cancer incidence in Spain, 2015 Galceran, J.; Ameijide, A.; Carulla, M. ...
Clinical & translational oncology,
07/2017, Letnik:
19, Številka:
7
Journal Article
Recenzirano
Purpose
Periodic cancer incidence estimates of Spain from all existing population-based cancer registries at any given time are required. The objective of this study was to present the current ...situation of cancer incidence in Spain.
Methods
The Spanish Network of Cancer Registries (REDECAN) estimated the numbers of new cancer cases occurred in Spain in 2015 by applying the incidence-mortality ratios method. In the calculus, incidence data from population-based cancer registries and mortality data of all Spain were used.
Results
In 2015, nearly a quarter of a million new invasive cancer cases were diagnosed in Spain, almost 149,000 in men (60.0%) and 99,000 in women. Globally, the five most common cancers were those of colon–rectum, prostate, lung, breast and urinary bladder. By gender, the four most common cancers in men were those of prostate (22.4%), colon–rectum (16.6%), lung (15.1%) and urinary bladder (11.7%). In women, the most common ones were those of breast (28.0%), colon–rectum (16.9%), corpus uteri (6.2%) and lung (6.0%). In recent years, cancer incidence in men seems to have stabilized due to the fact that the decrease in tobacco-related cancers compensates for the increase in other types of cancer like those of colon and prostate. In women, despite the stabilization of breast cancer incidence, increased incidence is due, above all, to the rise of colorectal and tobacco-related cancers.
Conclusion
To reduce these incident cancer cases, improvement of smoking control policies and extension of colorectal cancer screening should be the two priorities in cancer prevention for the next years.
The first influenza pandemic in more than 40 years was declared in 2009. We aimed to evaluate the beliefs of Spanish infectious diseases professionals regarding several aspects of 2009 A (H1N1) ...influenza once the epidemic waned. An online survey was designed and distributed among members of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC). The survey considered hospital organization and preparedness planning and conduct, as well as the opinion of the infectious diseases professionals regarding several key issues. Between 7 March and 22 March 2010, 303 responses, corresponding to 12.8% of the SEIMC membership, were received. Of the respondents, 48.2% were microbiologists and 42.3% were clinicians dealing with infectious diseases. Forty-one per cent of respondents did not believe that 2009 A (H1N1) influenza had a more severe presentation than other seasonal influenzas. Only 5% fully agreed that 2009 A (H1N1) influenza had a more severe presentation. Influenza planning was available in 69.7% of represented institutions before the arrival of 2009 A (H1N1) influenza, and was considered to be useful, to different extents, by most professionals. In most institutions (88.3%), a multidisciplinary team was created to coordinate local pandemic influenza actions. The most successful protocols were those provided by regional healthcare authorities, followed by those from the CDC. The most problematic issues regarding 2009 A (H1N1) influenza were the management of patients in the emergency room and the vaccination and awareness of healthcare professionals (HCPs) regarding infection control. Microbiological diagnosis and the availability of antivirals were the least problematic areas. Although the majority of surveyed infectious diseases professionals did not believe that 2009 A (H1N1) influenza had an especially severe presentation, most of them agreed with the way that this epidemic was managed in their institutions.
The main objective of our study was to describe the epidemiological and microbiological features of an oligoclonal hospital-wide outbreak caused by OXA-48-producing Enterobacteriaceae (OXA-48-PE). ...OXA-48 is a carbapenemase belonging to Ambler class D beta-lactamases, identified frequently in the Mediterranean and Southern European countries, and associated with several Enterobacteriaceae species. An outbreak of OXA-48-PE with a complex epidemic pattern was detected in January 2011. Initial control measures included contact precautions and the reinforcement of infection control practices, but despite all efforts made, the epidemiological situation hardly changed and new measures were implemented during 2013. An observational retrospective study was performed to describe the main features of the outbreak and to analyse the cumulative incidence (CI) trends. Eight hundred and 16 patients colonised or infected by OXA-48-PE were identified during the 2-year period (January 2013–December 2014), female 46%, mean age (s.d.), 71.6 (15.2). The samples isolated in the incident cases were rectal swabs (80%), urine samples (10.7%), blood samples (2.8%) and other clinical samples (6.6%). The most frequent OXA-48-PE was Klebsiella pneumoniae. Eleven different clones were identified, but K. pneumoniae sequence types 11 and 405 were predominant: ST11 (64.2%) and ST405 (29.3%). OXA-48-PE CI trend suffered a statistically significant change in August 2013, which continued the following months. Though we could not eradicate the outbreak, we observed a statistically significant drop in CI after an intervention for OXA-48-PE control, based on patient cohort, active surveillance, electronic alerts and reinforcement of infection control measures in a tertiary hospital.
Parkinson’s disease patients suffer from both motor and nonmotor impairments. There is currently no cure for Parkinson’s disease, and the most commonly used treatment, levodopa, only functions as a ...temporary relief of motor symptoms. Inhibition of the expression of the L‐tryptophan‐catabolizing enzyme tryptophan 2,3‐dioxygenase (TDO) has been shown to inhibit aging‐related α‐synuclein toxicity in Caenorhabditis elegans. To evaluate TDO inhibition as a potential therapeutic strategy for Parkinson’s disease, a brain‐penetrable, small molecule TDO inhibitor was developed, referred to as NTRC 3531‐0. This compound potently inhibits human and mouse TDO in biochemical and cell‐based assays and is selective over IDO1, an evolutionary unrelated enzyme that catalyzes the same reaction. In mice, NTRC 3531‐0 increased plasma and brain L‐tryptophan levels after oral administration, demonstrating inhibition of TDO activity in vivo. The effect on Parkinson’s disease symptoms was evaluated in a rotenone‐induced Parkinson’s disease mouse model. A structurally dissimilar TDO inhibitor, LM10, was evaluated in parallel. Both inhibitors had beneficial effects on rotenone‐induced motor and cognitive dysfunction as well as rotenone‐induced dopaminergic cell loss and neuroinflammation in the substantia nigra. Moreover, both inhibitors improved intestinal transit and enhanced colon length, which indicates a reduction of the rotenone‐induced intestinal dysfunction. Consistent with this, mice treated with TDO inhibitor showed decreased expression of rotenone‐induced glial fibrillary acidic protein, which is a marker of enteric glial cells, and decreased α‐synuclein accumulation in the enteric plexus. Our data support TDO inhibition as a potential therapeutic strategy to decrease motor, cognitive, and gastrointestinal symptoms in Parkinson’s disease.
Using two selective small molecule inhibitors, the inhibition of tryptophan 2,3‐dioxygenase (TDO) was validated as a potential new therapeutic approach for Parkinson's disease. In a rotenone‐induced mouse model of Parkinson's disease, TDO inhibitor treatment induced positive effects on central nervous system function. Moreover, in contrast to standard therapy, the TDO inhibitors acted peripherally on the intestinal phenotype by reducing the rotenone‐induced intestinal inflammatory response.
We report the first detection in space of the single deuterated isotopologue of methyldiacetylene, CH
2
DC
4
H. A total of 12 rotational transitions, with
J
= 8–12 and
K
a
= 0 and 1, were identified ...for this species in TMC-1 in the 31.0–50.4 GHz range using the Yebes 40m radio telescope. The observed frequencies allowed us to obtain, for the first time, the spectroscopic parameters of this deuterated isotopologue. We derived a column density of (5.5 ± 0.2) × 10
11
cm
−2
. The abundance ratio between CH
3
C
4
H and CH
2
DC
4
H is 24 ± 2. This ratio is similar to that found for the CH
3
C
3
N/CH
2
DC
3
N analogue system, which is 22 ± 2. We did not detect the deuterated species CH
3
C
4
D, which has already been observed in laboratory experiments. The detection of deuterated CH
3
C
4
H allows us to extend the discussion on the chemical mechanisms of deuterium fractionation at work in TMC-1 using a new gas-phase chemical model with multiply deuterated molecules. Introducing a possible deuterium exchange reaction between CH
3
CCH and atomic deuterium allows us to account for the CH
3
C
4
H/CH
2
DC
4
H abundance ratio.
Observations of IRC +10216 with the Yebes 40m telescope between 31 and 50 GHz have revealed more than 150 unidentified lines. Some of them can be grouped into a new series of 26 doublets, ...harmonically related with integer quantum numbers ranging from J up=54 to 80. The separation of the doublets increases systematically with J, i.e., as expected for a linear species in one of its bending modes. The rotational parameters resulting from the fit to these data are B = 290.8844 ± 0.0004 MHz, D = 0.88 ± 0.04 Hz, q = 0.1463 ± 0.0001 MHz. The rotational constant is very close to that of the ground state of HC9N. Ab initio calculations show an excellent agreement between these parameters and those predicted for the lowest energy vibrationally excited state, ν 19=1, of HC9N. This is the first detection, and complete characterization in space, of vibrationally excited HC9N. An energy of 41.5 cm-1 is estimated for the ν 19 state. In addition, 17 doublets of HC7N in the ν 15=1 state, for which laboratory spectroscopy is available, have been detected for the first time in IRC+10216. Several doublets of HC5N in its ν 11=1 state have been also observed. The column density ratio between the ground and the lowest excited vibrational states are ≈127, 9.5, and 1.5 for HC5N, HC7N, and HC9N, respectively. We find that these lowest-lying vibrational states are most probably populated via infrared pumping to vibrationally excited states lying at ≈600 cm-1. The lowest vibrationally excited states thus need to be taken into account to precisely determine absolute abundances and abundanceratios for long carbon chains. The abundance ratios N(HC5N)/N(HC7N) and N(HC7N)/N(HC9N) are 2.4 and 7.7 respectively.
We report the detection of methyl ketene towards TMC-1 with the QUIJOTE line survey. Nineteen rotational transitions with rotational quantum numbers ranging from J = 3 up to J = 5 and K-a <= 2 were ...identified in the frequency range 32.0-50.4 GHz, 11 of which arise above the 3 sigma level. We derived a column density for CH3CHCO of N=1.5 x 10(11) cm(-2) and a rotational temperature of 9 K. Hence, the abundance ratio between ketene and methyl ketene, CH2CO/CH3CHCO, is 93. This species is the second C3H4O isomer detected. The other, trans-propenal (CH2CHCHO), corresponds to the most stable isomer and has a column density of N=(2.2 +/- 0.3)x10(11) cm(-2), which results in an abundance ratio CH2CHCHO/CH3CHCO of 1.5. The next non-detected isomer with the lowest energy is cis-propenal, which is therefore a good candidate for future discovery. We have carried out an in-depth study of the possible gas-phase chemical reactions involving methyl ketene to explain the abundance detected, achieving good agreement between chemical models and observations.
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